Impacto da acessibilidade na adesão ao tratamento fisioterapêutico de pessoas convivendo com paraparesia espástica tropical: estudo qualitativo / Impact of accessibility on adherence to physiotherapeutic treatment of people living with tropical spastic paraparesy: qualitative study

INTRODUÇÃO: A Paraparesia Espástica Tropical / Mielopatia Associada ao HTLV-1 (HAM/TSP) apresenta alterações crônico-degenerativas que comprometem os indivíduos nas atividades diárias, principalmente aquelas ligadas à locomoção. A acessibilidade é um parâmetro importante para a adesão à fisioterapia nestas pessoas. OBJETIVO: investigar o impacto da acessibilidade na adesão ao tratamento fisioterapêutico em pessoas infectadas pelo HTLV-1, com HAM/TSP. MÉTODO: estudo com abordagem qualitativa, com 38 participantes, maiores de 18 anos, com diagnóstico confirmado de HAM/TSP. Excluídos aqueles com dificuldade de compreensão dos questionamentos ou de comunicação. Para a coleta das informações, foram realizados 11 grupos focais e 12 entrevistas semiestruturadas. Os depoimentos foram gravados e depois transcritos. As informações foram sistematizadas pela análise do conteúdo temática-Categorial. RESULTADOS: Após as análises dos grupos focais e entrevistas, emergiram as seguintes categorias: dificuldade de acesso, dependência externa (climática/de acompanhante), dependência financeira e dependência de consultas médicas. CONCLUSÃO: A precariedade da infraestrutura e acessibilidade na cidade de Salvador, além da condição econômica, mudanças climáticas e dificuldades ao acesso do Sistema Único de Saúde, impactam diretamente na adesão ao tratamento fisioterapêutico. O não comparecimento à fisioterapia pode afetar a evolução do tratamento e a saúde dessa população.

| INTRODUCTION: Tropical Spastic Paraparesis / Myelopathy Associated with HTLV-1 (HAM / TSP) presents chronic degenerative changes that compromise individuals in their daily activities, especially those related to locomotion. Accessibility is an important means of adhering to physical therapy for all these people. OBJECTIVE: To investigate the impact of accessibility on adherence to physical therapy treatment in people infected with HTLV-1 with HAM / TSP. METHOD: a study with a qualitative approach, with 38 participants, over 18 years old, with a confirmed diagnosis of HAM / TSP. Those with difficulty understanding the questionnaires or communicating were excluded. For the collection of information, 11 focus groups and 12 semi-structured changes were performed. The researcher herself recorded and then transcribed the statements. The analysis of thematic-Categorial content systematized the information. RESULTS: After analyzing the focus groups and related, the following categories emerged: access difficulty, external dependence (climatic/accompanying), financial dependence, and dependence on medical appointments. CONCLUSION: The precariousness of infrastructure and accessibility in the city of Salvador, in addition to the economic condition, climate change, and difficulties in accessing the Unified Health System, directly impact adherence to physical therapy treatment. Failure to attend physical therapy can affect the evolution of treatment and the health of this population.

Co-expression of HBZ, TAX and FOXp3 and HTLV-1-associated myelopathy/tropical spastic paraparesis development in HTLV-1-infected individuals: A systematic review

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been reported that the HTLV-1 proteins (specifically TAX and HBZ) can modulate FOXp3, resulting in an immune imbalance that can favor the progression of HAM/TSP. This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 mRNAs and/or viral proteins (TAX and HBZ) with the expression of mRNA and/or protein FOXp3 and their correlation with HAM/TSP development. This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors. After screening, six articles were included in this review. The studies suggested that TAX and HBZ have a directly proportional correlation with FOXp3 in individuals with HAM/TSP, which also presented an increased expression of FOXp3 compared to asymptomatic controls and/or healthy donors. This systematic review indicates that TAX and HBZ can interact with FOXp3 and that interaction may influence HAM/TSP development.

Impact of fractures and orthopedic surgeries in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis

Abstract INTRODUCTION In patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) gait disturbance is a predominant feature that leads to falls and fractures, which can further aggravate disability. We sought to evaluate the impact of fractures and orthopedic surgeries in patients with HAM/TSP. METHODS: We retrieved the medical records of HAM/TSP patients enrolled in our study center's HTLV-1 clinical cohort between 1989-2018. The selection criteria included: (1) diagnosis of HTLV-1 infection using two enzyme-linked immunosorbent assays and/or a confirmatory test, (2) clinical diagnosis of HAM/TSP by neurological assessment, and (3) fractures associated with HAM/TSP. RESULTS: We identified 24 cases of fractures, 70% of which were females. The median age at the time of fracture was 60 years (IQR=24). Six cases reported fractures in patients under 45 years old. Ten patients (42%) had hip/coccyx fractures, seven (29%) were in the lower extremities, and four (17%) in the upper extremities. Half of these patients reported the use of wheelchairs. Five patients who had previously used canes required the use of wheelchairs after the reported fracture. Eight patients underwent corrective orthopedic surgery as a result of the fracture. CONCLUSIONS: For HAM/TSP patients, fractures are a complication that can exacerbate their severe impairment.

Influence of proprioceptive neuromuscular facilitation on the muscle tonus and amplitude of movement in HTLV-1-infected patients with HAM/TSP

Abstract An HTLV-1-infected patient can develop paraparesis that limits their movements. Rehabilitation techniques could improve the motor abilities of these patients. The present study investigates five cases of physical therapy intervention in HTLV-1 patients to evaluate the influence of functional rehabilitation on the tonus and range of motion (ROM) of HTLV-1 patients with spasticity. The patients had a gain of ROM, especially in the lower limb, and reduction in hypertonia/spasticity after functional treatment. The reduction in hypertonia increased the ROM. Thus, functional methods may be valuable for the rehabilitation of HTLV-1 patients with neurological damage.

Re-emergence of human T-lymphotropic viruses in West Africa

ABSTRACT Human T-lymphotropic viruses (HTLV) are Deltaretroviruses that infect millions of individuals worldwide via the same transmission routes as HIV. With the aim of exposing the possible re-emergence of HTLV in West Africa since discovery, a systematic review was carried out, focusing on the distribution of the virus types and significance of frequent indeterminate reports, while highlighting the need for mandatory routine blood screening. Capturing relevant data from discovery till date, sources searched were Google Scholar, CrossRef, NCBI (PubMed), MEDLINE, Research Gate, Mendeley, abstracts of Conferences and Proceedings, organization websites and reference lists of selected papers. A total of 2626 references were initially retrieved using search terms: Worldwide prevalence of HTLV, HTLV in Africa, HTLV in West Africa, HTLV subtypes, HTLV 3 and 4 in Africa, HTLV of African origin, HTLV seroindeterminate results, Spread of HTLV. These references were rigorously trimmed down to 76. Although evidence shows that HTLV is still endemic in the region, West Africa lacks recent epidemiological prevalence data. Thorough investigations are needed to ascertain the true cause of indeterminate Western Blot results. It is imperative that routine screening for HTLVs be mandated in West African health care facilities.

The relationship between atopy and neurological manifestations in HTLV-1 infection

Abstract INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)induces exaggerated Th1 responses, whereas atopy is associated with exacerbated Th2 responses. METHODS: Here, a cross-sectional study compared the prevalence of atopy in HTLV-1 carriers and HAM/TSP patients. It also compared the spontaneous cytokine production in HTLV-1-infected individuals. A retrospective cohort study evaluated the development of neurological manifestations in atopic and non-atopic carriers. RESULTS: Atopic HAM/TSP patients with high IFN-γ production exhibited higher IL-5 levels than non-atopic patients. Allergic rhinitis accelerated the development of Babinski signals and overactive bladders. CONCLUSIONS: Abnormal Th1 and Th2 responses coexist in HTLV-1-infected individuals and allergic diseases may worsen the clinical course of HTLV-1 infections.

Cardiovascular risk profile in patients with myelopathy associated with HTLV-1

ABSTRACT HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) is a slowly progressive disease, characterized by a chronic spastic paraparesis. It is not known if the disease carries an independent risk for cardiovascular disease. The objective of this study was to evaluate the cardiovascular risk profile related to HAM/TSP and compare it with the general population. Methods: This was a cross-sectional study, with a control group. HAM/TSP patients were evaluated using cardiovascular risk scores (ASCVD RISK, SCORE and Framingham) and inflammatory markers (ultrasensitive CRP and IL-6), and compared with a control group of healthy individuals. We also evaluated the correlation between cardiovascular risk and the functional status of patients with HAM/TSP evaluated by the FIM scale. Results: Eighty percent of patients in this study were females, mean age of 51 years (11.3). The control group showed an increased cardiovascular event risk in 10 years when ASCVD was analyzed (cardiovascular risk ≥7.5% in 10 years seen in 43% of patients in the control group vs. 23% of patients with HAM/TSP; p = 0.037). There was no difference in ultrasensitive CRP or IL-6 values between the groups, even when groups were stratified into low and high risk. There was no correlation between the functional status of HAM/TSP patients and the cardiovascular risk. Conclusions: In this study, the cardiovascular risk profile of patients with HAM/TSP was better than the risk of the control group.

Clinical and laboratory features of HTLV-I asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis from the Brazilian Amazon

ABSTRACT Clinical and laboratory parameters including blood and cerebrospinal fluid (CSF) neopterin were investigated in human-T-lymphotropic-virus-type-I associated-myelopathy/tropical-spastic-paraparesis-HAM/TSP and in HTLV-I carriers. HAM/TSP (n = 11, 2 males/9 females, median age = 48 years), recently diagnosed HTLV-I carriers (n = 21, 15 females/6 males, median age = 44 years), healthy individuals (n = 20, 10 males/10 females, median age = 34.6 years) from the Brazilian Amazon (Manaus, Amazonas State) were investigated. Neopterin was measured (IBL ELISA Neopterin, Germany) in serum samples of all the participants, in CSF of 9 HAM/TSP patients as well as in 6 carriers. In HAM/TSP patients, CSF cell counts, protein and glucose were measured, the Osame’s motor-disability-score/OMDS was determined, and brain/spinal cord magnetic-resonance-imaging (MRI) was performed. HAM/TSP patients had normal CSF glucose, leukocyte counts; and normal protein levels predominated. Brain-MRI showed white-matter lesions in 7 out of 11 HAM/TSP patients. OMDS varied from 2-8: 9 were able to walk, 2 were wheel-chair-users. The median serum neopterin concentration in HAM/TSP patients was 6.6 nmol/ L; min. 2.8- max. 12.5 nmol/ L); was lower in carriers (4.3 nmol/L; min. 2.7- max. 7.2 nmol/ L) as well as in healthy participants (4.7 nmol/ L; min. 2.7- max. 8.0 nmol/ L) (p < 0.05). CSF neopterin concentrations in HAM/TSP patients were higher than in serum samples, and higher compared to carriers (p < 0.05). Carriers had similar serum-CSF neopterin concentrations compared to healthy participants. Variable clinical and laboratory profiles were seen in HAM/TSP patients, however our results support the neopterin measurement as a potential biomarker of disease activity.

Pain prevalence, characteristics and associated factors in human T-cell lymphotropic virus type 1 infected patients: a systematic review of the literature

ABSTRACT Objective: To describe the pain in patients infected with human T-cell lymphotropic virus type 1, clinically and epidemiologically. Methods: This systematic review was based on The PRISMA Statement. Four reviewers searched PUBMED, SciELO, LILACS and BIREME for data from observational studies and clinical trials (n ≥ 30) regarding pain prevalence, characteristics, and associated factors in patients with human T-cell lymphotropic virus type 1. No limits on publication date or language were established. Studies that did not have pain as an outcome measure or not involving human T-cell lymphotropic virus type 1 infected patients were excluded. Results: A total of 3013 articles (including duplicates) were found of which seven met the predetermined criteria. The most common pain region was the lower back (53.0%). Non-neuropathic type (ranging from 52.6% to 86.8%) was more frequent in human T-cell lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis participants, and neuropathic pain was more common in human T-cell lymphotropic virus type 1 carriers (53.1%). The pain was mostly reported as moderate or severe. One study showed that chronic pain was negatively associated with quality of life. Discussion: Pain is a common complaint in human T-cell lymphotropic virus type 1 infected patients, with lower back pain as the most frequent site. Pain can either be nociceptive, neuropathic, or both, is frequently severe, and negatively affects quality of life. Only studies of two countries were included in this review, limiting the external validity of the conclusions. The heterogeneity of variables prevented us from implementing a meta-analysis. Further research should better characterize the pain and explore its impact on quality of life, especially using longitudinal study design.

Muscular weakness represents the main limiting factor of walk, functional independence and quality of life of myelopathy patients associated to HTLV-1 / Fraqueza muscular representa o principal fator limitante da marcha, independência funcional e qualidade de vida de pacientes com mielopatia associada ao HTLV-1

ABSTRACT HTLV-1-associated myelopathy is a progressive disabling disease associated with gait abnormalities. Objective To identify and quantify the main muscles affected by weakness and spasticity, their impact on gait, functional capacity and on quality of life of HTLV-1-associated myelopathy patients. Method We evaluated lower limbs muscular strength according to the Medical Research Council scale, spasticity according to the modified Ashworth scale, daily activities according to the Barthel Index and quality of life according to the Short-Form Health Survey-36 of 26 HTLV-1-associated myelopathy patients. Results The muscles most affected by weakness included the dorsal flexors and knee flexors. Spasticity predominated in the hip adductor muscles and in plantar flexors. Assistance for locomotion, minimal dependence in daily activities, limitations in functional capacity and physical aspects were the most common findings. Conclusion The impairment of gait, functional dependence and quality of life were predominantly a consequence of intense muscle weakness in HTLV-1-associated myelopathy patients.

RESUMO Mielopatia associada ao HTLV-1 é uma doença inflamatória, incapacitante e progressiva que acomete o sistema nervoso central. Objetivo Identificar e quantificar os principais músculos comprometidos pela fraqueza e espasticidade, o impacto na capacidade funcional e na qualidade de vida dos pacientes com mielopatia associada ao HTLV-1. Método Força muscular ( Medical Research Council), espasticidade (escala Ashworth modificada), atividades de vida diária (Índice de Barthel) e qualidade de vida ( Short-Form Health Survey-36) foram avaliados em 26 pacientes . Resultados Os principais músculos comprometidos pela fraqueza incluíram os flexores dorsais e flexores do joelho. A espasticidade predominou nos músculos adutores do quadril e nos flexores plantares. Assistência para locomoção, dependência mínima nas atividades diárias, limitações na capacidade funcional e os aspectos físicos representaram os achados mais frequentes. Conclusão Dificuldade de deambulação, dependência funcional e prejuízo na qualidade de vida foram as principais consequências da intensa fraqueza muscular nos pacientes com mielopatia associada ao HTLV-1.

T cell receptor signaling pathway is overexpressed in CD4 + T cells from HAM/TSP individuals

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4+ T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3?), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta-chain (TCR) associated protein kinase 70 kDa (ZAP70) on T lymphocytes of HTLV-1-infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3?, LCK, ZAP70, and VAV1 gene expression were increased in CD4+ T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3?, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3?, LCK, and VAV1 gene expression in CD4+ T cells, and these genes function on a synchronized way on the CD4+ T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP.

Neurological aspects of HTLV-1 infection in Bahia: results from an 8-year cohort / Aspectos neurológicos da infecção pelo HTLV-1 na Bahia: resultados de uma coorte de 8 anos

HTLV-1 is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease observed in up to 5% of individuals infected with HTLV-1. However, infected individuals without the disease can present neurological complaints relating to sensory, motor or urinary manifestations. The aim of this study was to investigate the incidence of neurological manifestations among patients with HTLV-1. Method HTLV-1 patients in Salvador, Bahia, Brazil, were enrolled into a cohort study. Results Among 414 subjects, 76 had definite and 87 had possible or probable HAM/TSP at the baseline, whereas 251 subjects had no neurological signs or symptoms. Definite HAM/TSP developed in 5 patients (1.74%). The asymptomatic subjects were selected for analysis. The incidence rate expressed per 1,000 persons-year was calculated. It was 206 for hand numbness, 129 for nocturia and 126 for urinary urgency. In the neurological examination, leg hyperreflexia presented an average incidence rate of 76; leg paraparesis, 52; and Babinski sign, 36. Kaplan-Meyer curves categorized according to gender and proviral load showed that females and patients with proviral load of more than 100,000 copies per 106 peripheral blood mononuclear cells (PBMCs) presented higher risk. Conclusion Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects ...

Concentrações plasmáticas de citocinas e quimiocinas na infecção pelo HTLV-1 / Plasma concentrations of cytokines and chemokines in HTLV-1

INTRODUÇÃO: O vírus linfotrópico das células T humano tipo 1 (HTLV-1) é endêmico na Bahia e está associado com doenças graves, como a Paraparesia Espástica Tropical/Mielopatia associada ao HTLV-1 (HAM/TSP) e a Dermatite Infecciosa associada ao HTLV-1 (DIH). Escassos trabalhos tem sido reportados com a avaliação de citocinas e quimiocinas em indivíduos jovens infectados pelo HTLV-1 e não existem dados sobre a manifestação simultânea DIH e HAM/TSP na faixa infanto-juvenil. OBJETIVO: Avaliar as concentrações plasmáticas de citocinas e quimiocinas na infecção pelo HTLV-1 em indivíduos infanto-juvenis. MÉTODO: Foram incluídos 61 indivíduos portadores do HTLV-1 distribuídos nos grupos Portadores assintomáticos, pacientes com a DIH, pacientes com DIH/HAM/TSP, pacientes com a HAM/TSP e 20 indivíduos saudáveis sem a infecção pelo HTLV-1, todos na faixa infanto-juvenil. As concentrações plasmáticas foram comparadas através do método de Elisa e de Cytometric Bead Array (CBA)...

INTRODUCTION: The lymphotropic virus of cells T human type 1 (HTLV ) is endemic in Bahia and it is associated with serious diseases such as Tropical Spastic Paraparesis/associated myelopathy with HTLV-1 and Infectious Dermatitis associated with HTLV -1 (IDH). Very little work has been reported with the evaluation of cytokines and chemokines in the IDH and there has been no data on the manifestation simultaneous IDH and HAM/TSP in children and youth range. OBJECTIVE: To evaluate the plasma concentrations of cytokines and chemokines in HTLV-1 infection in children and young individuals. METHOD: We included 61 individuals HTLV-1 spread in groups Asymptomatic Carriers, patients with IDH, patients with IDH/HAM/TSP, patients with HAM/TSP and 20 healthy individuals without HTLV-1, all in children's range. Plasma concentrations were compared using the ELISA method and Cytometric Bead Array (CBA)...

Interferon beta11a treatment in htlv-1-associatd myelopathy/tropical spastic pparaparesis: a case report / Tratamento com interferon beta-1a em mielopatia associada ao HTLV-1/paraparesia espástica tropical: relato de caso

Here a young patient (< 21 years of age) with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF). Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.

Descreve-se caso de mielopatia associada ao HTLV-1/paraparesia espástica tropical tratada com interferon beta-1a em paciente jovem de 21 anos e com história de dermatite infecciosa na infância. Foi estabelecida clinicamente paraparesia espástica tropical (HAM/TSP), confirmada laboratorialmente pela presença de anticorpos para HTLV-1 no LCR e excluídas caxumba, citomegalovirus, Epstein-Barr, esquistossomose, herpes virus 1 e 2, rubéola, sarampo, toxoplasmose varicela-zoster, hepatite, HIV e sífilis por sorologias. Foi diagnosticada bexiga neurogênica, com quadro clínico de nictúria, urgência urinária, parestesia no membro inferior esquerdo e discreta redução de força muscular nos membros superiores, mais acentuada nos membros inferiores. Na 4a semana de tratamento com interferon beta-1a houve desaparecimento da urgência urinária e da parestesia e melhora da clínica motora.

Avaliação fenotípica e funcional dos linfócitos T citotóxicos de indivíduos infectados pelo HTLV-1 com diagnóstico de HAM/TSP / Phenotypic and functional assessment of cytotoxic T lymphocytes from individuals infected with HTLV-1 diagnosed with HAM / TSP

O Brasil representa uma das áreas endêmicas para o vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) e a cidade de Salvador, Bahia, possui a maior prevalência nacional da infecção por este retrovírus (1,8%), com cerca de 50.000 pessoas infectadas. O HTLV-1 foi o primeiro retrovírus humano descrito e está classicamente associado à leucemia/linfoma de células T do adulto (ATLL) e à mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). A HAM/TSP é uma doença inflamatória do sistema nervoso central, cujos mecanismos imunopatogênicos não estão completamente elucidados. O papel dos linfócitos T citotóxicos na patogênese desta doença ainda não está bem definido. Neste estudo, foram avaliados o fenótipo e a função de linfócitos T citotóxicos de pacientes infectados pelo HTLV-1 com HAM/TSP...

Brazil represents one of the largest endemic areas for human T-lymphotropic virus cells type 1 (HTLV-1) infection and associated diseases. Salvador, Bahia, is considered as the Brazilian city with the highest national HTLV-1prevalence (around 1.8% in the general population). HTLV -1 was the first human retrovirus described and is classically associated with adult Tcell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic and progressive inflammatory disease of the central nervous system and your immunopathogenic mechanisms are not completely understood. The role of cytotoxic T-lymphocytes (CTLs) in the pathogenesis of this disease is still undefined. In this study we evaluated the phenotype and function of cytotoxic Tlymphocytes from HTLV-1-infected patients with HAM/TSP...

Associação dos genes KIR2DL2K/KIR2DL3 e alelos de HLA-C do grupo 1 com a mielopatia associada ao HTLV-1/Paraparesia espástica tropical (HAM/TSP) / Association of KIR2DL2K / KIR2DL3 genes and HLA-C group 1 alleles with HTLV-1 associated myelopathy / Tropical spastic paraparesis (HAM / TSP)

O controle da carga proviral do HTLV-1 depende em parte da lise de células infectadas por células citotóxicas mediada pelos linfócitos T CD8⁺ e pelas células NK (Natural killer). A família de receptores KIR (killer-cell immunoglobulin-like receptor) interage com as moléculas de HLA de classe I, principalmente os alelos do HLA C do grupo 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 e C*16), ativando ou inibindo a função destas células.O objetivo do presente estudo foi avaliar se os genes KIR2DL2/KIR2DL3 e os alelos de HLA-C do grupo 1 estão associados ao controle da carga proviral do HTLV-1 e ao diagnóstico de HAM/TSP. O estudo foi realizado no Centro de HTLV da Escola Bahiana de Medicina e Saúde Púbica, em Salvador-Bahia. A presença dos genes KIR2DL2 e KIR2DL3 foi determinada por PCR em tempo real (Syber Green). Foram incluídos 248 indivíduos infectados pelo HTLV-1 (161 assintomáticos e 87 com HAM/TSP) cujos alelos de HLA de classe I haviam sido previamente determinados. A carga proviral (quantificada por PCR em tempo real) e as frequências de indivíduos assintomáticos e com diagnóstico de HAM/TSP (Possível, Provável e Definido) foram comparadas de acordo com a presença ou ausência dos genes KIR avaliados. As frequências dos genes KIR2DL2 e KIR2DL3 foi 84,3% e 96,8%...

The control of proviral load of HTLV-1 depends in part of the lysis of infected cells mediated by cytotoxic CD8⁺T lymphocytes and NK (Natural killer) cells. The family of KIR (killer-cell immunoglobulin-like receptor) interacts with HLA class I molecules, especially those HLA-C alleles in-group 1 (C*01, C*03, C*07, C*08, C*12, C*13, C*14 and C*16) by activating or inhibiting the function of these cells. The aim of this study was to evaluate if the KIR2DL2, KIR2DL3 genes and group 1 HLA-C alleles are associated with the control of proviral load of HTLV-1 and the diagnosis of HAM/TSP. The study was performed at Bahiana School HTLV Center of Medicine and Health Public, in Salvador, Bahia. The presence of KIR2DL2 and KIR2DL3 genes was determined by real-time PCR (Syber Green). The study included 248 subjects infected with HTLV-1(161 and 87 asymptomatic with HAM/TSP) whose HLA class I alleles were previously determined. The proviral load (quantified by real-time PCR) and the frequency asymptomatic individuals diagnosed with HAM/TSP (possibly, probably and definitive) were compared according to the presence or absence of KIR genes evaluated. The frequencies of KIR2DL2 and KIR2DL3 genes were 84.3% and 96.8%...

Aportes y consideraciones sobre la infección por los virus linfotrópicos-T humanos tipo 1 y 2 en Argentina / Contributions to the knowledge of Human T-Cell Lymphotropic Virus Type 1 and 2 (HTLV-1/2) infections in Argentina

El virus linfotrópicos-T humanos tipo 1 (HTLV-1) es el agente etiológico de una enfermedad hematológica de mal pronóstico, la leucemia de células T del adulto (ATL) y de una enfermedad neurológica invalidante, la mielopatía asociada al HTLV-1/paraparesia espástica tropical (HAM/TSP) para las cuales no existe un tratamiento eficaz. El virus linfotrópico-T humano tipo 2 (HTLV-2) ha sido relacionado a síndromes neurológicos, aumento de infecciones y mortalidad. En Argentina, existe una restricción étnica/geográfica con una región endémica para el HTLV-1 en el Noroeste (Aymarás) y otra para el HTLV-2 en la Región Chaqueña (Tobas y Wichis). El aumento de corrientes migratorias a partir de áreas endémicas ha contribuido a la mayor circulación de estos virus en el país, hecho que plantea el desafío de poder brindar un diagnóstico final y una atención integral a los individuos. Este manuscrito comprende una revisión actualizada y la experiencia de nuestro grupo sobre estas infecciones...

HTLV-1 is the ethiologic agent of an hematologic disease with bad prognosis, Adult T-cell Leukemia (ATL) lethal in short time and a chronic and progressively invalidant neurological disease, HTLV-1 Associated Mielopathy/Tropical Spastic Paraparesis (HAM/TSP), for which no effective treatment is available. HTLV-2 has been related to neurologic syndromes, an increase in infections and mortality. In Argentina, the infection shows an ethnic/geographic restriction with an endemic regions for HTLV-1 in the Northeast (Aymaras) and for HTLV-2 in the Chaqueña Region (Tobas y Wichis). The increasing migrations from endemic areas have contributed to a major circulatin of these viruses and detection of HAM/TSP and ATL cases countrywide. This situation poses the challenge of giving a complete and final diagnosis and an integral care to infected individuals. This manuscript describes general aspects of HTLV-1/2 and the situation and experience of our group on these infections in the country...

Perfil de ativação dos linfócitos T de pacientes com mielopatia associada ao vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) / paraparesia tropical espástica (HAM/TSP) possível, provável e definido / Activation profile of T lymphocytes of patients with myelopathy associated with human T-lymphotropic virus type 1 cells (HTLV-1) tropical spastic paraparesis (HAM / TSP) possible, probable and definite

O vírus linfotrópico das células T humanas do tipo 1 (HTLV-1) é o agente etiológico da mielopatia associada ao HTLV / paraparesia espástica tropical (HAM / TSP ), que ocorre em menos de 5 % dos indivíduos infectados. A resposta imune controla parcialmente a infecção, porém pode estar ligada a patogênese da doença. O objetivo deste estudo foi caracterizar fenotipicamente as subpopulações de linfócitos T, em pacientes assintomáticos e com diagnóstico de HAM/TSP. Foram avaliados 103 pacientes acompanhados no Centro de HTLV da Escola Bahiana de Medicina e Saúde Pública (EBMSP) e 19 controles não infectados. Os pacientes foram categorizados de acordo com o grau de certeza do diagnóstico de HAM/TSP: possível (Ps), provável (Pb) e definido (D), além de pacientes assintomáticos (ASS). O perfil fenotípico (CD25, CD45RA, CD45RO, HLA-DR, CD25, CCR-7, CD62L)...

The human T-cell lymphotropic vírus type 1(HTLV-1) is the etiological agent of HTLV- associated myelopathy/ Tropical spastic paraparesis(HAM/TSP), wich occurs in less then 5% of the infected individuals. The immune response partially controls the infection, but may be linked to the pathogenesis of disease. The aim of this study was to characterize phenotipically T lymphocyte subpopulations in asymptomatic and in patients diagnosed with HAM/TSP. We evaluated 103 patients treated at the center for HTLV of Bahia School of Medicine and Public Health (EBMSP) and 19 uninfected controls. Patients were categorized as asymptomatic and according to the degree of certainty of the diagnosis of HAM/TSP: Possible(Ps), Probable(Pb) and Definite(D). The phenotypic profile (CD25, CD45RA, CD45RO, HLA-DR, CCR-7, CD62L)...

Estudo da influência dos alelos do HLA classe I e II e do polimorfismo dos genes de citocinas na infecção pelo HTLV-1 / Study of the influence of hla class i and ii alleles and the polymorphism of cytokines genes in htlv-1 infection

O vírus linfotrópico para células T humanas (HTLV-1) é o principal agente causador da Paraparesia Espástica Tropical / Mielopatia associada ao HTLV-1 (PET/MAH) e da Leucemia da célula T do Adulto (LTA). [...]Fatores da interação HTLV-1/ hospedeiro estão envolvidos no risco de desenvolver doença. A lesão neurológica na PET/MAH parece ser consequência de uma reação inflamatória, desencadeada pelo reconhecimento de células infectadas por linfócitos T citotóxicos, com consequente liberação de citocinas e lesão medular. OBJETIVO: Identificar marcadores genéticos, que possam ajudar no prognóstico e tratamento dos pacientes portadores do HTLV-1. MÉTODOS: Nas amostras de 117 portadores do HTLV-1 assintomáticos e 171 pacientes com acometimento neurológico em acompanhamento na cidade do Rio de Janeiro, foram realizadas as tipificações dos genes do HLA Classe I e II, dos polimorfismos dos genes das citocinas -308TNF-α,-174IL-6, +874IFN-γ, códon 10 e 25TGF-β1 e -1082 - 819-592IL-10, e a quantificação da carga proviral. Os dados foram organizados em um banco de dados no programa SPSS. As frequências alélicas e genotípicas foram obtidas por contagem direta. O equilíbrio de Hardy-Weinberg foi avaliado para os polimorfismos das citocinas no sitio http://bioinfo.iconcologia.net/ubbweb/SNPStats_web, em relação ao HLA foram utilizadas as ferramentas disponíveis no sítio “Los Alamos HIV database tools”. As comparações entre os grupos foram realizadas através de tabelas de contingência 2x2 (quiquadrado, exato de Fisher e odds ratios), valores de p≤0,05 foram considerados significantes...

The human T cell lymphotropic vírus (HTLV-1) is the main causingagent of Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (HAM/TSP) aswell as of Adult T Cell Leukemia (ATL). [...] Factorsrelated to the HTLV-1/host interaction may be involved in the risk of developing thediseases. The neurological lesion in HAM/TSP may be the consequence of aninflammatory reaction, triggered by the recognition of infected cells by cytotoxic Tlymphocytes, followed by the release of cytokines and central nervous system lesion.OBJECTIVE: This work aims to identify genetic markers, which may help in theprognosis and treatment of HTLV-1 patients. Methods: The polymorphism of the HLAClass I and II genes, as well as the TNF-α, IL6, IFN-γ, TGF-β and IL-10 cytokinegenes, and the proviral load were analysed in 117 asymptomatic HTLV-1 carriersand 171 HTLV-1 symptomatic carriers from Rio de Janeiro city. Data were organizedinto a database using SPSS. The Hardy-Weinberg equilibrium was evaluated forcytokine polimorphisms using the site http://bioinfo.iconcologia.net/ubbweb/SNPStats_web. The tools available in the site “Los Alamos HIV database tools” were used toanalyze the HLA polimorphisms. Comparisons between groups were made using 2x2contingency tables (Fisher Exact test/ χ2 and odds ratios), p values p≤0,05 wereconsidered significant...

Contribution of Galvanic Vestibular Stimulation for the Diagnosis of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

BACKGROUND AND PURPOSE: Galvanic vestibular stimulation (GVS) is a low-cost and safe examination for testing the vestibulospinal pathway. Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive disease that affects the vestibulospinal tract early in its course. This study compared the electromyographic (EMG) responses triggered by GVS of asymptomatic HTLV-1-infected subjects and subjects with HAM/TSP. METHODS: Bipolar galvanic stimuli (400 ms and 2 mA) were applied to the mastoid processes of 39 subjects (n=120 stimulations per subject, with 60 from each lower limb). Both the short latency (SL) and medium latency (ML) components of the EMG response were recorded from the soleus muscles of 13 healthy, HTLV-1-negative adults (56+/-5 years, mean+/-SD), and 26 individuals infected with HTLV-1, of whom 13 were asymptomatic (56+/-8 years) and 13 had HAM/TSP (60+/-6 years). RESULTS: The SL and ML EMG components were 55+/-4 and 112+/-10 ms, respectively, in the group of healthy subjects, 61+/-6 and 112+/-10 ms and in the HTLV-1-asymptomatic group, and 67+/-8 and 130+/-3 ms in the HAM/TSP group (p=0.001). The SL component was delayed in 4/13 (31%) of the examinations in the HTLV-1-asymptomatic group, while the ML component was normal in all of them. In the HAM/TSP group, the most common alteration was the absence of waves. CONCLUSIONS: A pattern of abnormal vestibular-evoked EMG responses was found in HTLV-1-neurological disease, ranging from delayed latency among asymptomatic carriers to the absence of a response in HAM/TSP. GVS may contribute to the early diagnosis and monitoring of nontraumatic myelopathies.