The importance of confirmatory assays in testing blood donors for human T-cell lymphotropic virus.

BACKGROUND AND OBJECTIVES: Serological HTLV-1/2 screening is mandatory for blood donor candidates in Brazil. Our objective was to analyse HTLV test results in blood donors submitted for screening and confirmatory assays in a Brazilian blood bank. MATERIALS AND METHODS: Retrospective analysis (2017-2022) results of chemiluminescence immunoassays and confirmatory tests for HTLV-1/2 in reactive donors were performed. During the analysed period, three sets of assays were used: (1) Architect rHTLV-I/II + HTLV Blot 2.4 (Western blot [WB]); (2) Alinity s HTLV I/II Reagent Kit + INNO-line immunoassay (LIA) HTLV I/II Score (LIA); (3) Alinity + WB. RESULTS: The analysed period comprised a total of 1,557,333 donations. The mean percentage of HTLV reactive donors using the Architect assay was 0.14%. With the change to the Alinity assay, that percentage dropped 2.3-fold (0.06%). The reactivity rate in the confirmatory tests (1064 samples) ranged from 13.5% to 30.2%, whereas 58.3%-85.9% of samples were non-reactive. The highest rates of positive (30.2%) and indeterminate (11.5%) results were seen using LIA. Considering all analysed samples, those with signal/cut-off ratio (S/CO) >50 were positive in confirmatory tests (positive predictive value, PPV = 100%), whereas samples with S/CO ≤6 are very unlikely to be truly positive (PPV = 0). CONCLUSION: The use of the Alinity assay reduced the frequency of false-positive results. Confirmatory tests are important to identify true HTLV infection in blood donors, because more than 58% of initially reactive individuals are confirmed as seronegative. Categorizing S/CO values is useful for assessing the likelihood of true HTLV-1/2 infection.

Diagnostic accuracy of Abbott Architect Assay as a screening tool for human T-cell leukaemia virus type-1 and type-2 infection in a London teaching hospital with a large solid organ transplant centre.

AIM: In the United Kingdom, organ donors/recipients are screened for evidence of human T-cell leukaemia virus type-1 and type-2 (HTLV-1/2) infections. Since the United Kingdom is a low prevalence country for HTLV infections, a screening assay with high sensitivity and specificity is required. Samples with repeat reactivity on antibody testing are sent to a reference lab for confirmatory serological and molecular testing. In the case of donor screen, this leads to delays in the release of organs and can result in wastage. We aim to assess whether a signal/cut-off (S/CO) ratio higher than the manufacturer's recommendation of 1.0 in the Abbott Architect antibody assay is a reliable measure of HTLV-1/2 infection. METHODS: We conducted a 5 year retrospective analysis of 7245 patients from which 11 766 samples were tested on the Abbott Architect rHTLV I/II assay. Reactive samples (S/CO >1) were referred for confirmatory serological and molecular detection (Western Blot and proviral DNA) at UK Health Security Agency, (formerly PHE, Colindale), the national reference laboratory. Electronic, protected laboratory and hospital patient databases were employed to collate data. RESULTS: A total of 45 patients had initially reactive samples. 42.2% (n = 19/45) had an S/CO ratio > 20, with HTLV infection confirmed in n = 18/19 and indeterminate confirmatory results in n = 1/19. No samples with an S/CO ratio <4 (48.9%, n = 22/45) or 4-20 (8.9%, n = 4/45) had positive confirmatory results on subsequent confirmatory testing. CONCLUSION: Samples with an S/CO >20 likely represent a true HTLV-1/2 infection. Reactive samples with an S/CO <4 were unlikely to confirm for HTLV infections. Interpretation of these ratios can assist clinicians in the assessment of low reactive samples and reiterates the need for faster access to confirmatory testing.

Estimation of the window period of human T-cell leukemia virus type 1 and 2 tests by a lookback study of seroconverters among Japanese voluntary blood donors.

BACKGROUND: Japan is endemic for human T-cell leukemia virus type 1 (HTLV-1), and the horizontal transmission of HTLV-1 is often reported. However, the window period (WP) for serologic or molecular screening is unclear. STUDY DESIGN AND METHODS: Results for anti-HTLV-1 screening and confirmatory tests obtained from 648 591 repeated blood donors in the Kyushu district, one of the most endemic areas of HTLV-1 in the world, were evaluated. A lookback study was conducted for seroconverters. RESULTS: During 2012 to 2019, 436 seroconverters (155 men, 281women) were identified with use of a screening chemiluminescence enzyme-immunoassay (CLEIA) and multiple confirmatory tests. Because the period between the latest seronegative donation and seroconversion was highly variable (2.1-276.7 months), 19 cases that seroconverted within 6 months were subjected to the analysis. The WP of the particle agglutination assay and CLEIA was estimated to be 2.2 ± 0.6 and 2.6 ± 1.7 months, respectively. The WP of the indirect immunofluorescence assay was 4.8 ± 6.5 months. Although the WP of western blotting was estimated to be 6.3 ± 8.7 months, four cases were still indeterminate through the study period. Chemiluminescence and line immunoassays, the current screening and confirmatory tests used in the Japanese blood program, showed the shortest WP of 2.2 ± 0.6 months. The WP of real-time polymerase chain reaction for HTLV-1 was estimated to be 4.1 ± 7.8 months. CONCLUSIONS: The WP in commercially available testing systems for HTLV-1/2 was determined for natural infection among repeated blood donors. Considering the HTLV-1 WP will help increase transfusion safety and facilitate the accurate diagnosis of HTLV-1 infection.

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil.

HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.

Isolation of the Arawete and Asurini Indians keeps the tribes free from HTLV infection during 36 years of follow-up.

Arawete and Asurini Indian tribes were revisited after a 36-year follow-up in search of HTLV infections. 46 persons (23 from each tribe) were tested for HTLV-1/2 antibodies and viral DNA. None were positive; this was probably because of their social/cultural isolation from neighboring tribes where HTLV-2c is hyperendemic.

Seroprevalence of human T-lymphotropic virus (HTLV) in blood donors in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Human T-cell lymphotropic viruses (HTLV) 1 and 2 are endemic in sub-Saharan Africa (SSA), transfusion-transmissible and causally linked to various severe diseases. However, even in SSA countries with moderate to high endemicity, routine blood donor screening for HTLV is rarely, if ever, performed. Information on seroprevalence is limited. The aim of this review is to establish the prevalence of HTLV-1 and HTLV-1/2 among blood donors in sub-Saharan Africa. MATERIALS AND METHODS: We systematically reviewed databases including EMBASE, MEDLINE and the Cochrane database library from their inception to June 2018. Studies presenting data on HTLV prevalence among blood donors in sub-Saharan Africa were included. A random-effect meta-analysis was conducted on all eligible studies. RESULTS: A total of 25 studies were included, representing 74 119 blood donors, of whom over 80% (61 002) were only tested for HTLV-1. The evidence base was high and moderate in quality. The pooled prevalence of the 17 studies that screened only for HTLV-1 and the nine studies that screened for HTLV-1/2 was 0·68 (95% CI: 0·29-1·60) and 1·11 (95% CI: 0·47-2·59) per 100 blood donors, respectively. CONCLUSION: The prevalence of HTLV-1 infection among blood donors is relatively low. The current review is intended to inform debates and decisions about best practices to prevent transfusion-transmitted HTLV in sub-Saharan Africa. Further work is required to determine the risk of infections by transfusion and the cost-effectiveness of any new measures such as routine screening.

[Detection of Human T lymphotropic virus 1 (HTLV-1) Cosmopolitan subtype Transcontinental subgroup (Aa) and HTLV-2 subtype b in blood donors of Corrientes]. / Hallazgo del virus linfotrópico T humano 1 (HTLV-1) subtipo Cosmopolita subgrupo Transcontinental (Aa) y del HTLV-2 subtipo b en donantes de sangre de Corrientes.

A molecular epidemiological study was conducted in a population of 9422 blood donors in the province of Corrientes, Northeastern Argentina, to determine the prevalence of Human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2), the phylogenetic identification of HTLV-1 and 2 subtypes/subgroups and perform a mutation analysis. Based on the results obtained, it was shown that both HTLV-1 and HTLV-2 are circulating in a low-risk population of Corrientes, although with a similar prevalence to that of non-endemic areas. Phylogenetic studies identified the HTLV-1 Cosmopolitan subtype Transcontinental subgroup (Aa), and the HTLV-2 subtype b. Infected donors reported neither a history of risk factors such as transfusions, intravenous drug use, nor risky or HTLV-1/2 seropositive sexual partners. These results suggest that these viruses were transmitted from mother to child, possibly from generation to generation, and that these strains were introduced into the Caucasian population of this region from ancestors originating from endemic areas of the country either from or through contact with individuals from other countries years ago. Our results demonstrate for the first time the presence of HTLV-1 and HTLV-2 in the province of Corrientes. Moreover, although the province can be considered a non-endemic area, the need to include these retroviruses in a national Public Health program is highlighted, in order to have qualified professionals duly trained to make their diagnosis and provide the necessary information in relation to primary care and patient follow-up.

Hepatitis B, C, and D virus and human T-cell leukemia virus types 1 and 2 infections and correlates among men who have sex with men in Ouagadougou, Burkina Faso.

BACKGROUND: Men who have sex with men (MSM) are considered to be at significant risk for sexually transmitted infections (STI) and bloodborne viruses including viral hepatitis types B, C, and D (HBV, HCV, and HDV) and human T-cell leukemia virus types 1 and 2 (HTLV 1&2). This study aimed to assess the seroprevalence and correlates of HBV, HCV, HDV, and HTLV 1&2 antibodies among MSM in Ouagadougou, Burkina Faso. METHODS: We conducted a cross-sectional survey to assess the biological and behavourial characteristics among MSM in Ouagadougou from January to April 2013. Serum specimens obtained were tested for the presence of HBV, HCV, HDV and HTLV-1&2 infections. MSM 18 years and older were recruited using respondent driven sampling (RDS). Population estimates and 95% confidence intervals (CI) adjusted for the RDS design were calculated using RDS Analysis Tool (RDSAT) version 6.0.1 (RDS, Inc., Ithaca, NY). Bivariate and multivariate logistic regression analyses were conducted to assess correlates of these infections using Stata 14. RESULTS: A total of 329 MSM were tested. Prevalence was 20.4% (95% CI: 16.4-25.1) for HBV, 11.0% (95% CI: 8.0-14.8) for HCV, and 0.0% for HDV. Anti-HTLV 1&2 antibodies were found in 4.0% (95% CI: 2.3-6.8) of MSM. Factors independently associated with HBV infection were lack of condom use during the last anal sex act with a main male sexual partner and experience of condom tearing during anal sex. Presence of anti-HTLV 1&2 antibodies was associated with history of genital or anal lesions and injection drug use. None of the variables included in our study were associated with HCV. CONCLUSIONS: This study shows that HBV, HCV and HTLV 1&2 prevalence among MSM in Burkina is high and suggests that comprehensive STI prevention and sexual health education services for this group are needed.

Human parvovirus 4 prevalence among HTLV-1/2 infected individuals in Brazil.

Human parvovirus 4 (PARV4), a Tetraparvovirus, has been largely found in HIV, HBV, or HCV infected individuals. However, there is no data for the PARV4 occurrence in Human T-lymphotropic virus (HTLV-1/2) infected individuals, despite similar transmission routes. Here, PARV4 viremia was evaluated in 130 HTLV infected patients under care of a Brazilian HTLV outpatient clinic. PARV4 viremia was detected in 6.2% of the HTLV-1 infected patients. Most PARV4 positives showed no evidence for parenterally transmitted infections. It is suggested that in Brazil, transmission routes of PARV4 are more complex than in Europe and North America and resemble those in Africa. J. Med. Virol. 89:748-752, 2017. © 2016 Wiley Periodicals, Inc.

First description of HTLV-1/2 seroprevalence in HIV-infected inmates in Mozambique.

No study has yet been conducted to estimate the burden of co-infection of HIV and HTLV-1/2 in inmates in sub-Saharan Africa. To investigate prevalence of co-infection in inmates in Mozambique, a total of 2140 inmates were screened for HIV, of which 515 were HIV seropositive. All HIV seropositive inmates were further screened for HTLV infection, and eight (1.55%) were co-infected. Co-infection was higher in females (3.45% [2/58; CI: 0.42-11.91]) as compared to males (1.35% [6/445; CI: 0.55-3.06]). Early screening of HTLV in prisons is urgently needed in Mozambique in order to improve the care provided to incarcerated individuals, including initiation of ART.