Seroprevalence of Human T-cell Lymphotropic Virus Types I/II Among Blood Donors in a Tertiary Hospital in Oman.

Objectives: Routine blood donor screening of human T-cell lymphotropic virus (HTLV) has been practiced in Oman since 2017. Limited data exists on HTLV seroprevalence among Omanis. This study aims to determine the seroprevalence of HTLV-I/II among blood donors attending a hospital-based blood bank to assess the need for a universal versus targeted screening. Methods: We conducted a retrospective review of blood donors' results attending a hospital blood bank between January 2017 and February 2020. Blood samples were screened for HTLV-I/II antibodies using ARCHITECT i2000SR. Reactive samples underwent further testing by immunoblot assay (MP Diagnostics HTLV Blot 2.4). Age, gender, and nationality were assessed. All components manufactured at the blood bank undergo leukoreduction before storage. Results: A total of 24 469 first-time blood donors were screened for HTLV antibodies. Most participants were male (n = 22 186, 90.7%), and the majority were Omani (n = 22 711, 92.8%). The age range was 18 to 64 years, with a median of 32 years. The seroreactivity rate was 0.2% (43; 95% CI: 0.12-0.23). Confirmatory testing by immunoblot revealed three indeterminate results (7.9%), of which two were Omani and one non-Omani donor, and the remaining 40 seroreactive donors tested negative. Conclusions: Our study revealed zero seroprevalence of confirmed HTLV among blood donors. The continuation of universal screening for first-time donors is a standard of care. With universal leukoreduction at Sultan Qaboos University Hospital and a very low risk of HTLV in Oman's population, the need for screening regular donors can be reconsidered if these findings are confirmed on a larger scale involving other blood banks in Oman.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Physiotherapy Methods Applied in the Prevention of Functional Loss Associated with Human T-Lymphotropic Virus 1 Infection: An Overview.

To achieve the objective of this study, we conducted a narrative review on physical therapeutic modalities applied to prevent functional losses associated with human T-lymphotropic virus 1 (HTLV-1) infections to promote health education and viable and accessible alternatives in the development of health education technology adapted to the home environment. This study comprised a qualitative stage of theoretical development to construct a digital booklet with an observational basis based on studies that reiterate themes about educational technologies as tools to conduct a home protocol of guided exercises without the direct supervision of professional physical therapists. Results indicate a lack of research on the development of health education technologies to assist patients with HTLV-1 without tropical spastic paraparesis or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We believe that this narrative review can initiate a theoretical framework to conduct a home exercise program aimed at people with HTLV-1 who have subtle symptoms, and also at people without the clinical definition of HAM/TSP, helping to train human resources for care and research on the subject and increase scientific production in physical therapy.

COVID-19 y leucemia/linfoma T del adulto, sinergia mortal / COVID-19 and adult T cell leukemia-lymphoma: a deadly synergy

La leucemia/linfoma T del adulto es una neoplasia maligna de mal pronóstico frecuente en población anciana. Se presenta el caso de una mujer de 44 años de edad, de Ayacucho, diagnosticada con el subtipo linfomatoso de esta enfermedad e infección por virus linfotrópico T humano-I; mostró síndrome oclusivo de vena cava superior con tratamiento de quimioterapia sistémica bajo régimen de dosis ajustada con rituximab más etoposido, prednisona, vincristina, ciclofosfamida y doxorubicina. Posteriormente ingresó en emergencia por presentar dificultad respiratoria, tos seca, disminución de la conciencia, hipercalcemia, tomografía de tórax con patrón heterogéneo consolidativo en ambos pulmones y PCR en hisopado nasofaríngeo positivo a COVID-19. Recibió tratamiento de hidroxicloroquina, azitromicina, corticoides e ivermectina con pobre respuesta, rápido deterioro y fallece días después. La leucemia/linfoma T del adulto a edad temprana es rara y está relacionada con infecciones crónicas como strongyloides o tuberculosis, susceptible ante el padecimiento de COVID-19.

Adult T cell leukemia-lymphoma is a common malignancy with a poor prognosis in the elderly population. We present a 44-year-old woman from Ayacucho who was diagnosed with a lymphoma subtype of this disease and a human T-lymphotropic virus-I infection; she showed superior vena cava occlusive syndrome with systemic chemotherapy treatment under an adjusted-dose regimen with rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin. Subsequently, she was admitted to the emergency service due to respiratory distress, dry cough, decreased consciousness, hipercalcemia, chest tomography with a heterogeneous consolidation pattern in both lungs and positive RT-PCR nasopharyngeal swab test for COVID-19. She received treatment with hydroxychloroquine, azithromycin, corticosteroids and ivermectin with a poor response, rapid deterioration and died later. Adult T cell leukemia-lymphoma at an early age is rare and is related to chronic infections such as strongyloides or tuberculosis, susceptible to COVID-19.

Pentraxin 3, a serum biomarker in human T-cell lymphotropic virus type-1-associated myelopathy patients and asymptomatic carriers.

Human T-cell lymphotropic virus type 1 (HTLV-1) can induce a neuroinflammatory condition that leads to myelopathy. Pentraxin 3 (PTX3) is an acute-phase protein that its plasma concentration increases during inflammation. We aimed to determine whether PTX3 serum level is elevated in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-1 asymptomatic carriers (ACs) and evaluate its association with proviral load and clinical features. The serum level of PTX3 was measured using an enzyme-linked immunosorbent assay in 30 HAM patients, 30 HTLV-1 ACs, and 30 healthy controls. Also, the HTLV-1 proviral load was determined via real-time PCR technique. The findings showed that PTX3 serum level was significantly higher in HAM patients than in both asymptomatic carriers and healthy controls (p values < 0.0001). No correlation between PTX3 and the proviral load was observed in HAM patients and asymptomatic carriers (r = - 0.238, p = 0.205 and r = - 0.078, p = 0.681, respectively). The findings showed that there was no significant correlation between PTX3 and motor disability grading (MDG) (r = - 0.155, p = 0.41) nor urinary disturbance score (UDS) (r = - 0.238, p = 0.20). Higher levels of PTX3 are associated with HTLV-1-associated myelopathy compared to asymptomatic carriers. This finding may support the idea that PTX3 has the potential as a diagnostic biomarker.

Distribución geográfica y tipo de infección del virus linfotrópico T humano en pacientes peruanos 2019-2021

En el presente estudio describimos y caracterizamos la distribución geográfica de los casos positivos confirmados a HTLV-1 y 2 de pacientes peruanos con diagnóstico presuntivo entre 2019 y 2021. De un total de 555 muestras positivas confirmadas, 546 (98,4%) fueron HTLV-1 y 9 (1,6%) HTLV-2. Además, 22 de 24 departamentos del Perú presentaron casos de HTLV-1, siendo los principales motivos de solicitud de confirmación diagnóstica: aspirante a donar sangre con prueba de tamizaje reactivo, sospecha de leucemia/linfoma y paraparesia espástica tropical. Los resultados reflejan que la identificación de los puntos críticos constituye una brecha persistente respecto al diagnóstico, siendo cruciales para reducir el número de nuevos casos en Perú.

In the present study we describe and characterize the geographic distribution of HTLV-1 and 2 positive cases from Peruvian patients with presumptive diagnosis 2019 - 2021. Of a total of 555 confirmed positive samples, 546 (98.4%) were HTLV-1 and 9 (1.6%) HTLV-2. In addition, 22 of 24 departments of Peru presented cases of HTLV-1. The main reasons for requesting a confirmatory diagnosis being: aspiring to donate blood with a reactive screening test, suspicion of leukemia/ lymphoma and tropical spastic paraparesis. The results reflect that the identification of critical points constitutes a persistent gap regarding the diagnosis, being crucial to reduce the number of new cases in Peru.

Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skills / Idosos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1apresentam comprometimento precoce em habilidades cognitivas

Abstract Background Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1 )-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1. Objective To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years. Methods This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests. Results Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group. Conclusions Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.

Resumo Antecedentes Alterações cerebrais ocorrem em indivíduos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1 (HTLV-1) (HAM) e parecem predominar em áreas subcorticais. Pouco se sabe sobre o declínio cognitivo em idosos vivendo com HTLV-1. Objetivo Avaliar o envelhecimento cognitivo de indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos. Métodos Trata-se de um estudo transversal com ex-doadores de sangue infectados pelo HTLV-1 acompanhados na coorte do Grupo Interdisciplinar de Pesquisa em HTLV-1 há 20 anos. Os grupos de estudo foram compostos por 79 indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos, sendo que 41 apresentavam HAM e 38 eram portadores assintomáticos, e 59 indivíduos soronegativos (controles) com idade ≥ 60 anos. Todos foram submetidos ao teste eletrofisiológico P300 e testes neuropsicológicos. Resultados Indivíduos com HAM apresentaram atraso na latência do P300 em relação aos demais grupos, e esse atraso de latência aumentou progressivamente com o envelhecimento. O desempenho desse grupo nos testes neuropsicológicos também foi o pior. O desempenho do grupo HTLV-1- assintomático foi semelhante ao do grupo controle. Conclusão Indivíduos com HAM apresentaram declínio cognitivo que progrediu com o envelhecimento e, embora os portadores assintomáticos do HTLV-1 pareçam apresentar envelhecimento cognitivo semelhante ao dos idosos saudáveis, justificase a preocupação com um comprometimento cognitivo subclínico nessa população.

Impaired flexibility in patients with tropical spastic paraparesis/HTLV-associated myelopathy: evaluation via pendulum fleximeter / Flexibilidade prejudicada em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV: avaliação via flexímetro pendular

Abstract Background Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility. Objective To evaluate the differences in flexibility between HTLV-1-infected individuals with and without myelopathy compared with uninfected controls. We also investigated whether age, sex, body mass index (BMI), physical activity level, or lower back pain influence flexibility in HTLV-1-infected individuals. Methods The sample consisted of 56 adults, of which 15 did not have HTLV-1, 15 had HTLV-1 without myelopathy, and 26 had TSP/HAM. Their flexibility was assessed using the sit-and-reach test and a pendulum fleximeter. Results No differences in flexibility were observed between the groups with and without myelopathy and controls without HTLV-1 infection using the sit-and-reach test. The pendulum fleximeter results of individuals with TSP/HAM presented the lowest flexibility among the groups with respect to trunk flexion, hip flexion and extension, knee flexion, and ankle dorsiflexion, even after adjusting for age, sex, BMI, level of physical activity, and lower back pain using multiple linear regression models. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced flexibility in movements: knee flexion, dorsiflexion, and ankle plantar flexion. Conclusions Individuals with TSP/HAM demonstrated reduced flexibility in most of the movements evaluated by the pendulum fleximeter. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced knee and ankle flexibility, potentially representing a marker of myelopathic development.

Resumo Antecedentes A flexibilidade é fundamental para a execução harmoniosa dos movimentos articulares. Embora a disfunção do músculo esquelético em pacientes com HTLV-1 possa interferir na mobilidade, não está claro se esses pacientes apresentam flexibilidade reduzida. Objetivo Avaliar as diferenças de flexibilidade entre os indivíduos infectados com e sem mielopatia e o grupo controle sem infecção HTLV-1. Também investigamos se idade, sexo, índice de massa corporal (IMC), nível de atividade física ou dor lombar influenciam a flexibilidade em indivíduos infectados pelo HTLV-1. Métodos A amostra foi composta por 56 adultos, dos quais 15 não possuíam HTLV-1, 15 possuíam HTLV-1 sem mielopatia e 26 possuíam TSP/HAM. A flexibilidade foi avaliada por meio do teste de sentar e alcançar e do flexímetro de pêndulo. Resultados Não foram observadas diferenças na flexibilidade entre os grupos com e sem mielopatia no teste de sentar e alcançar. Os resultados do flexímetro pendular dos indivíduos com TSP/HAM apresentaram a menor flexibilidade entre os grupos em relação à flexão do tronco, flexão e extensão do quadril, flexão do joelho e dorsiflexão do tornozelo, mesmo após ajuste para idade, sexo, IMC, nível de atividade física e dor lombar usando modelos de regressão múltipla linear. Além disso, os indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade nos movimentos de flexão do joelho, dorsiflexão e flexão plantar do tornozelo. Conclusão Indivíduos com TSP/HAM demonstraram redução da flexibilidade na maioria dos movimentos avaliados pelo flexímetro pendular. Além disso, indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade do joelho e tornozelo, representando potencialmente um marcador de desenvolvimento mielopático.

A human T-lymphotropic virus-1 carrier who developed progressive multifocal leukoencephalopathy following immunotherapy for sarcoidosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disorder of the central nervous system caused by opportunistic infection of the JC virus (JCV). CASE PRESENTATION: A 58-year-old Japanese woman was admitted to our hospital for aphasia. She had a 5-year history of untreated sarcoidosis and was a human T cell lymphotropic virus-1 (HTLV-1) carrier. Serum angiotensin-converting enzyme, soluble interleukin-2 receptor, lysozyme, and calcium levels were elevated. JCV-DNA was not detected in cerebrospinal fluid by PCR testing. Skin biopsy revealed noncaseating granuloma formation. Bilateral multiple nodular lesions were present on chest X-ray. Brain magnetic resonance imaging showed left frontal and temporal lesions without gadolinium enhancement. As we suspected that systemic sarcoidosis had developed into neurosarcoidosis, we started steroid and infliximab administration. After treatment, the chest X-ray and serum abnormalities ameliorated, but the neurological deficits remained. At 1 month after immunotherapy, she developed right hemiparesis. Cerebrospinal fluid was positive for prototype (PML-type) JCV on repeated PCR testing. Brain biopsy revealed demyelinating lesions with macrophage infiltration, atypical astrocytes, and JCV antigen-positive cells. We diagnosed her with PML and started mefloquine, leading to partial remission. CONCLUSIONS: Sarcoidosis and HTLV-1 infection both affect T cell function, especially CD4+ T cells, and may developped the patient's PML. The comorbidity of sarcoidosis, PML, and HTLV-1 infection has not been reported, and this is the world's first report of PML associated with HTLV-1 infection and sarcoidosis.

Evolution of erectile dysfunction in individuals infected with human T-lymphotropic virus 1: a prospective cohort study.

BACKGROUND: Virtually all patients with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have some degree of erectile dysfunction (ED), but ED is also found in a large percentage of HTLV-1 carriers. AIM: To evaluate the evolution of ED in individuals infected with HTLV-1 who were followed for up to 15 years. METHODS: This prospective cohort study included men infected with HTLV-1 who had ED, were aged 18 to 70 years, and were followed from January 2004 to December 2019. We used the International Index of Erectile Function-5 (IIEF-5), the Expanded Disability Status Scale and Osame Motor Disability Scale, and the Overactive Bladder Symptom Score (OABSS) to define and stratify ED, neurologic disability, and bladder dysfunction, respectively. OUTCOMES: Time to development of severe ED was the main outcome. RESULTS: We studied 90 men with ED (mean ± SD age, 52.8 ± 9.78 years). At baseline, 42 were carriers, 16 had probable HAM/TSP, and 32 had definite HAM/TSP. IIEF-5 was highest among carriers and lowest in patients with definite HAM/TSP, whereas OABSS was lowest in carriers and highest in patients with definite HAM/TSP. Median (IQR) follow-up was 8.50 years (3.00-12.00). IIEF-5 fell significantly from baseline to last follow-up among carriers and patients with probable and definite HAM/TSP. There was an inverse correlation between the IIEF-5 and the OABSS at last follow-up (r = -0.62, P < .001). In survival analysis, the time to development of severe ED was significantly shorter in patients with definite HAM/TSP when compared with carriers (P = .001) and those with probable HAM/TSP (P = .014). The presence of definite HAM/TSP at baseline was independently associated with the development of severe ED, after adjustment for baseline age and proviral load (hazard ratio, 6.74; P = .008). CLINICAL IMPLICATIONS: Formal assessment of erectile function should be part of the routine clinical assessment of individuals infected with HTLV-1; worsening erectile function should alert clinicians to the possibility of neurologic deterioration. STRENGTHS AND LIMITATIONS: This is the first prospective cohort study to describe the course of ED in men infected with HTLV-1. The small sample size and absence of seronegative controls are limitations. CONCLUSION: ED is a slowly progressive clinical manifestation of HTLV-1 infection, and the degree of neurologic compromise at baseline is the main predictor of time to progression to severe ED.

Development and validation of a duplex real-time PCR for the rapid detection and quantitation of HTLV-1.

BACKGROUND: The HTLV-1 prevalence in China varies geographically, while HTLV-2 infection has rarely been found so far. Proviral load is one of the determining factors of pathogenesis and progression of HTLV-1 related diseases. However, neither molecular assays nor commercial kits are available for HTLV-1 diagnosis in China. The objective of the present study was to develop and validate a TaqMan qPCR assay for HTLV-1 proviral load quantification. RESULTS: A plasmid containing both the HTLV-1 of interest and a fragment of the RNase P (RPPH1) gene was constructed and used to establish the standard curves. The assay has a wide dynamic range (2.5 × 108 copies/reaction ~ 25 copies/reaction) and sensitive to 1 copy for HTLV-1 and RPPH1. The limit of detection for Hut102 cell concentration was 0.0218% (95% confidence interval 0.0179-0.0298%). The assay gave coefficient of variation (CV) for both the HTLV-1 and RPPH1 Ct values. All of the HTLV-1 sero-negative samples and MOT cell line (infected with HTLV-2) amplified only the RPPH1 gene by our method, presenting 100% specificity. 85 Samples confirmed positive or indeterminate by LIA were performed by established qPCR assay and WB. 90.0% (27/30) of LIA-HTLV-1-positive, 33% (2/6) of LIA-untypeable and 2% (1/49) of LIA-indeterminate samples were defined as qPCR-positive. The median PVL of LIA-positive samples (n = 27, 1.780 copies/100 cells) was much higher than that of LIA-untypeable and (n = 2, 0.271 copies/100 cells) indeterminate samples (n = 1, 0.017 copies/ 100 cells). Additionally, compared to WB, the duplex qPCR verified more positive samples, demonstrating a better sensitivity. CONCLUSION: The duplex qPCR developed here with high sensitivity, good specificity and reproducibility could accurately and quantitatively detect the HTLV-1 PVLs, which can be used to confirm the initial reactive samples for an improved cost/benefit ratio as well as to monitor the clinical progression and efficacy of therapy in patients with HTLV-1 related disease.

XCL1, a serum biomarker in neurological diseases; HTLV-1-associated myelopathy and multiple sclerosis.

The XCL1-XCR1 axis has a potential role in the recruitment of immune cells to the site of inflammation. The present study aimed to examine the relation of XCL1 serum levels with Multiple sclerosis (MS) and HTLV-1-associated myelopathy (HAM), as chronic inflammatory diseases of the central nervous system (CNS). DNA was extracted to evaluate HTLV-1 proviral load (PVL) using real-time PCR. Serum levels of XCL1 was determined by using an ELISA assay. The serum level of XCL1 was significantly higher in patients with HAM than that of asymptomatic carriers (ACs) and healthy controls (HCs) (p < 0.001 and p < 0.0001, respectively) and was also higher in MS patients compared to HCs (p < 0.0001). Moreover, the concentration of XCL1 serum level was significantly different between the ACs and HCs group (p < 0.0001). In conclusion, increased expression of XCL1 might contribute to the migration of autoreactive T cells to the central nervous system and play a critical role in the development and pathogenesis of inflammatory neurological diseases including HAM and MS.

T cell receptor repertoire analysis in HTLV-1-associated diseases.

Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4+ T cells in vivo which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8+ T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.

Identification of hub genes and molecular pathways in human T-lymphotropic virus type 1 associated diseases using protein-protein interactions networks.

Background and Objectives: Human T-lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study aims to analyze gene expression patterns in ATL and HAM/TSP. Materials and Methods: Microarray gene expression profiling of T-lymphocytes from HTLV-1 associated disease and healthy control were obtained from Gene Expression Omnibus (GEO). Several bioinformatics tools were used to identify differentially expressed genes (DEGs). Among the generated DEGs, we constructed protein-protein interaction (PPI) between HAM/TSM and ATL in comparison to asymptomatic carriers (ACs). Subsequently, gene ontology (GO) and topological analysis were performed. Results: We found that the majority of DEGs in ATL and HAM/TSP were importantly implicated in immune response categories. The nodes and edges number of normal-AC, AC-ATL and ATL-HAM/TSP PPIs were 168 and 145, 116 and 97, and 275 and 327, respectively. Based on the topological analyses of protein-protein interaction networks, APP (Amyloid Beta Precursor Protein) was detected as a critical player in progression of HTLV-1 disease. Conclusion: Dysregulation of immune response associated transcripts play a critical role in HTLV-1 disease progression. Immune response associated genes may be biomarker for prognosis in cancer development and therapeutic targets.

Autoimmune manifestations in pediatric patients with human type I T - cell lymphotropic virus (HTLV-1) infection / Manifestaciones autoinmunes en pacientes pediátricos con infección por virus linfotrópico humano de células T tipo I (HTLV-1)

ABSTRACT HTLV-1 is a retrovirus that has an impact on human health due to its T-lymphocyte tropism. It occurs worldwide, but is more prevalent in tropical regions. Although most infected individuals will remain asymptomatic, the infection may manifest with complications such as uveitis, myelopathy, and leukemia, among others. The diagnosis is a chieved by the detection of anti-HTLV antibodies and a confirmatory test (Western Blot or proviral load). Although there is no specific treatment, medical treatments are aimed towards the management of secondary diseases. Three cases are described of pediatric patients diagnosed with HTLV-1 infection and associated autoimmune manifestations.

RESUMEN El virus linfotrópico humano de células T tipo I (HTLV-1) es un retrovirus que causa impacto en la salud del ser humano debido al tropismo para infectar a linfocitos T. Está distribuido mundialmente, pero es más prevalente en regiones tropicales. La mayoría de las personas afectadas permanecen asintomáticas, sin embargo, al manifestarse puede causar complicaciones como uveítis, mielopatía y leucemia, entre otras. Su diagnóstico se hace mediante la determinación de anticuerpos anti-HTLV y prueba confirmatoria (Western Blot o carga proviral). No tiene tratamiento específico, las medidas están dirigidas a la prevención y el manejo de las afecciones secundarias. Se describen tres pacientes en edad pediátrica con diagnóstico de infección por HTLV-1 y manifestaciones autoinmunes.

HTLV-1 Is Also a Sexually Transmitted Infection.

HTLV-1 is a retrovirus which causes diverse diseases in 10% of its infected population, significantly worsening their quality of life and mortality rate. Even though it is globally distributed and is endemic in many countries (including Peru), it is still highly neglected. It spreads through vertical, sexual and parenteral transmission. As no effective treatment against this virus exist, prevention is required to contain it. The World Health Organization published a technical report on the matter in 2021, with the collaboration of international HTLV-1 experts. However, neither the impact of sexual transmission (cause of the majority of adult cases and infection in non-endemic areas) nor its prevention were considered. Evidence is presented, which shows the magnitude of sexual transmission, its risk factors and preventive measures; hoping it will encourage health workers to help eradicate this infection.

Evaluation of Strongyloides stercoralis infection in patients with HTLV-1. / Evaluación de la infestación por Strongyloides stercoralis en pacientes con HTLV-1

INTRODUCTION: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response. OBJECTIVE: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil. MATERIALS AND METHODS: We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot. RESULTS: The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). CONCLUSIONS: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.

Introducción. Los individuos infectados por el virus linfotrópico T humano tipo 1 (HTLV-1) pueden presentar formas graves y diseminadas de infestación por Strongyloides stercoralis con poca mejoría terapéutica. Objetivo. Investigar la infestación por S. stercoralis y la seroprevalencia de IgG anti-S. stercoralis en individuos infectados por HTLV-1 atendidos en el Centro de Referencia para HTLV-1 (CHTLV), en Salvador, Bahía, Brasil. Materiales y métodos. Se hizo un estudio transversal con 178 individuos infectados por HTLV-1 atendidos en el centro especializado de HTLV entre enero de 2014 y diciembre de 2018. El diagnóstico parasitológico de S. stercoralis se hizo mediante los métodos de Hoffman, Pons y Janer, cultivo en placa de agar y Baermann-Morais. Para la detección de IgG anti-S. stercoralis, se utilizó una prueba casera de inmunoabsorción ligada a enzimas (ELISA). La infección por HTLV-1 se diagnosticó usando un ELISA comercial y se confirmó mediante Western blot. Resultados. La frecuencia de infestación por S. stercoralis fue del 3,4 % (6/178). Además, los individuos infestados por S. stercoralis provenientes de la zona rural (50,0 %; 3/6) también mostraron hiperinfestación por S. stercoralis (>3.000 larvas/gramo de heces). La frecuencia de anticuerpos IgG anti-S. stercoralis fue del 20,8 % (37/178). Conclusiones. Las personas infectadas por HTLV-1 que viven en condiciones sanitarias precarias son más propensas a desarrollar formas graves de infestación por S. stercoralis. Teniendo en cuenta la gran vulnerabilidad y el resultado desfavorable de la infección en estos individuos, se debe considerar el diagnóstico serológico de S. stercoralis para administrar el tratamiento.

Updates on the Epidemiology of the Human T-Cell Leukemia Virus Type 1 Infection in the Countries of the Eastern Mediterranean Regional Office of the World Health Organization with Special Emphasis on the Situation in Iran.

BACKGROUND: The epidemiology and prevalence of the Human T-cell leukemia virus type-1 (HTLV-1) infection represent a recommended priority by global health agencies. An in-depth revision to update the status of this infection in countries including those of the Eastern Mediterranean Regional Office (EMRO) of the World Health Organization is hence required. METHODS: Ninety-seven studies evaluating the HTLV-1 infection in low- and high-risk populations in EMRO countries were retrieved from the international electronic databases and were used to assess the epidemiological status of the infection in these countries. RESULTS: Most epidemiologic reports were published from Iran, with more than 50% of Iranian prisoners and around 4% of healthy individuals reported to have the infection. In Egypt, a considerable prevalence of the virus spans around 1.11% of blood donors. Foci of HTLV-1 infection are also present in some countries and require a careful epidemiological evaluation. In the other EMRO countries, a lower prevalence that does not exceed 1% was reported. CONCLUSION: The epidemiology and prevalence of HTLV-1 in the EMRO countries require a tight revision and update. Published studies reveal a scarce distribution of the virus in the African countries of EMRO, while a lower prevalence is denoted in the Asian countries of EMRO, except in Iran, where the prevalence is high.

Association of the rs4143815 polymorphism of PDL1 gene with HTLV-1 infection and proviral load in asymptomatic blood donors in northeast Iran.

It is obvious that genetic differences, including mutations and polymorphisms, can play an important role in viral infections. In this case-control study, which included 81 human T-cell leukemia virus type 1 (HTLV-1) asymptomatic carriers (AC) and 162 healthy controls (HC), the rs4143815 polymorphism of PDL1 gene was investigated. This polymorphism is the site of miR-570 binding and it can influence immune system responses. The rs4143815 polymorphism was evaluated by allele-specific polymerase chain reaction (AS-PCR) and the proviral load levels by quantitative real-time PCR (q PCR). The results demonstrated that the C allele (P = 0.027) and the CC genotype (P = 0.031) of rs4143815 polymorphism was significantly higher in the AC group than in the HC group, also the proviral load in the AC group with the C allele (P = 0.020) was significantly higher. Thus, the rs4143815 polymorphism can play a vital role in HTLV-1 infection.

Evaluation of Strongyloides stercoralis infection in patients with HTLV-1 / Evaluación de la infestación por Strongyloides stercoralis en pacientes con HTLV-1

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response. Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil. Materials and methods: We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot. Results: The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S . stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.

Introducción. Los individuos infectados por el virus linfotrópico T humano tipo 1 (HTLV-1) pueden presentar formas graves y diseminadas de infestación por Strongyloides stercoralis con poca mejoría terapéutica. Objetivo. Investigar la infestación por S. stercoralis y la seroprevalencia de IgG anti-S. stercoralis en individuos infectados por HTLV-1 atendidos en el Centro de Referencia para HTLV-1 (CHTLV), en Salvador, Bahía, Brasil. Materiales y métodos. Se hizo un estudio transversal con 178 individuos infectados por HTLV-1 atendidos en el centro especializado de HTLV entre enero de 2014 y diciembre de 2018. El diagnóstico parasitológico de S. stercoralis se hizo mediante los métodos de Hoffman, Pons y Janer, cultivo en placa de agar y Baermann-Morais. Para la detección de IgG anti-S. stercoralis, se utilizó una prueba casera de inmunoabsorción ligada a enzimas (ELISA). La infección por HTLV-1 se diagnosticó usando un ELISA comercial y se confirmó mediante Western blot. Resultados. La frecuencia de infestación por S. stercoralis fue del 3,4 % (6/178). Además, los individuos infestados por S. stercoralis provenientes de la zona rural (50,0 %; 3/6) también mostraron hiperinfestación por S. stercoralis (>3.000 larvas/gramo de heces). La frecuencia de anticuerpos IgG anti-S. stercoralis fue del 20,8 % (37/178). Conclusiones. Las personas infectadas por HTLV-1 que viven en condiciones sanitarias precarias son más propensas a desarrollar formas graves de infestación por S. stercoralis. Teniendo en cuenta la gran vulnerabilidad y el resultado desfavorable de la infección en estos individuos, se debe considerar el diagnóstico serológico de S. stercoralis para administrar el tratamiento