RESUMO
Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Linfócitos T CD4-Positivos/imunologia , Paraparesia Espástica Tropical/imunologia , Interferon gama/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos B Reguladores/imunologia , Linfócitos T CD4-Positivos/virologia , Paraparesia Espástica Tropical/virologia , Linfócitos T Reguladores/virologia , Linfócitos T CD8-Positivos/virologia , Carga Viral , Linfócitos B Reguladores/virologiaRESUMO
Abstract INTRODUCTION: Human T-cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may lead to reduced functional mobility and balance. It is important to establish specific parameters that identify these changes and predict the risk of falls in these patients. The aim was to compare balance, functional mobility, and occurrence of falls among patients with and without HAM/TSP and to suggest values to predict the risk of falls in these patients. METHODS: A cross-sectional study in patients with and without HAM/TSP involved balance assessments based on the berg balance scale (BBS) and functional mobility evaluation based on the timed up and go (TUG) test. From reports of falls, the sensitivity, specificity, and best cutoff points for the risk of falls assessed by these instruments were established using the receiver-operating characteristic (ROC) curve; 5% alpha was considered. RESULTS: We selected 42 participants: 29 with HAM/TSP and 13 without HAM/TSP. There was a statistically significant difference in the occurrence of falls, balance, and functional mobility between the groups (p<0.05). Good accuracy was determined for the BBS (77%) and TUG test (70%) and the cutoff points for the risk of falls were defined as 50 points for the BBS and 12.28 seconds for the TUG test. CONCLUSIONS: Patients with HAM/TSP present reduced functional mobility and balance in relation to those without HAM/TSP. The risk of falls increased for these patients can be evaluated by the values of 50 points using the BBS and 12.28 seconds using the TUG test.
Assuntos
Humanos , Masculino , Feminino , Adulto , Acidentes por Quedas/estatística & dados numéricos , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/complicações , Transtornos de Sensação/fisiopatologia , Equilíbrio Postural/fisiologia , Limitação da Mobilidade , Fatores Socioeconômicos , Atividades Cotidianas , Paraparesia Espástica Tropical/fisiopatologia , Paraparesia Espástica Tropical/virologia , Métodos Epidemiológicos , Transtornos de Sensação/virologia , Avaliação da DeficiênciaRESUMO
Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (ID) is a chronic, severe and recurrent eczema occurring during childhood in patients vertically infected with HTLV-1. HTLV-1-associated myelopathy/tropical spastic paraparesia (HAM/ TSP) is slow and progressive. We report the case of an adolescent female from a non-endemic area for HTLV-1 who presents ID and, most likely, associated HAM/TSP.
.Assuntos
Adolescente , Feminino , Humanos , Dermatite/virologia , Infecções por HTLV-I/complicações , Paraparesia Espástica Tropical/virologia , Dermatopatias Virais/virologia , Progressão da Doença , Dermatite/patologia , Infecções por HTLV-I/patologia , Imuno-Histoquímica , Paraparesia Espástica Tropical/patologia , Dermatoses do Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/virologia , Dermatopatias Virais/patologiaRESUMO
The retrovirus human T lymphotropic virus type 1 (HTLV-1) promotes spastic paraparesis, adult T cell leukaemia and other diseases. Recently, some human microRNAs (miRNAs) have been described as important factors in host-virus interactions. This study compared miRNA expression in control individuals, asymptomatic HTLV-1 carriers and HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis patients. The proviral load and Tax protein expression were measured in order to characterize the patients. hsa-miR-125b expression was significantly higher in patients than in controls (p = 0.0285) or in the HAM group (p = 0.0312). Therefore, our findings suggest that miR-125b expression can be used to elucidate the mechanisms of viral replication and pathogenic processes.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Produtos do Gene tax/metabolismo , MicroRNAs/metabolismo , Paraparesia Espástica Tropical/metabolismo , Biomarcadores/metabolismo , Portador Sadio , Estudos de Casos e Controles , Citometria de Fluxo , Vírus Linfotrópico T Tipo 1 Humano/crescimento & desenvolvimento , Paraparesia Espástica Tropical/virologia , Regulação para Cima , Carga Viral , Replicação ViralRESUMO
INTRODUCTION: Variations in human T cell lymphotropic virus type 1 (HTLV-1) proviral load (PVL) in infected individuals over time are not well understood. Objective: To evaluate the evolution of proviral load in asymptomatic individuals and HAM/TSP patients in order to help determine periodicity for measuring proviral load. METHODS: A group of 104 HTLV-1 infected patients, followed at the HTLV reference center in Salvador, Brazil, were included in the study (70 asymptomatic and 34 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients). HTLV-1 PVL was measured using real-time polymerase chain reaction (PCR) at baseline and again at another point, either < 12 months, between 12-24 months, or > 24 months. RESULTS: HAM/TSP patients had higher PVL (ranging from 11,041 to 317,009 copies/10(6) PBMC) when compared to asymptomatic individuals (ranging from 0 to 68,228 copies/10(6) PBMC). No statistically significant differences were observed in the medians of PVL in HAM/TSP patients or asymptomatic individuals over time. However, in asymptomatic individuals with a PVL below 50,000 copies/10(6) PBMC, a statistically significant two-fold increase was observed over time. CONCLUSION: HTLV-1-PVL remained stable in both asymptomatic individuals and HAM/TSP patients over time. Frequent monitoring of asymptomatic individuals with low PVLs is recommended and further studies should be conducted to assess the course of PVL in these patients over extended periods of time.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , DNA Viral/sangue , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Provírus/fisiologia , Carga Viral/fisiologia , Progressão da Doença , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/virologia , Provírus/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos RetrospectivosRESUMO
This review follows the contributions of researchers from the Caribbean in improving the understanding of the disease mechanisms, clinical features and aetiology of neurological syndromes manifesting as diseases of the spinal cord and peripheral nerves. The evolution from the initial descriptions of neuropathies of presumed nutritional aetiology and later the recognition of two distinct subgroups, an ataxic neuropathy and a spastic myelopathy, are highlighted. The link between the natural history of human T-cell leukaemia/lymphoma virus type-1 (HTLV-1) infection and the immunopathogenesis of tropical spastic paraparesis is explored.
Este examen sigue las contribuciones de investigadores del Caribe encaminadas a mejorar la comprensión de los mecanismos de la enfermedad, rasgos clínicos y la etiología de los síndromes neurológicos que se manifiestan como enfermedades de la médula espinal y los nervios periféricos. El trabajo resalta la evolución de las descripciones iniciales de las neuropatías de etiología nutricional presuntiva y el posterior reconocimiento de dos subgrupos claramente distintos: la neuropatía atáxica, y la mielopatía espástica. Se explora el vínculo entre la historia natural de la infección por el virus humano de células tipo 1 (HTLV-1) en la leucemia/linfoma, y la inmunopatogénesis de la paraparesia espástica tropical.
Assuntos
Humanos , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Doenças do Sistema Nervoso Periférico/virologia , Doenças da Medula Espinal/virologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/patologia , Jamaica , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologiaRESUMO
OBJETIVO: Caracterizar el ambiente genómico de las secuencias adyacentes al virus linfotrópico humano de células T tipo 1 (HTLV-1) en pacientes con paraparesia espßstica tropical y mielopatía asociada a la infección con HTLV-1 (PET/MAH) de diferentes regiones de Colombia y del Japón. MÉTODOS: Se enfrentaron 71 clones recombinantes con secuencias del genoma humano adyacentes al 5'-LTR de pacientes con PET/MAH, a las bases de datos del Genome Browser y del Gen-Bank. Se identificaron y analizaron estadísticamente 16 variables genómicas estructurales y composicionales mediante el programa informßtico R, versión 2.8.1, en una ventana de 0,5 Mb. RESULTADOS: El 43,0 por ciento de los provirus se localizaron en los cromosomas del grupo C; 74 por ciento de las secuencias se ubicaron en regiones teloméricas y subteloméricas (P < 0,05). Un anßlisis de conglomerados permitió establecer las relaciones jerßrquicas entre las características genómicas incluidas en el estudio; el anßlisis de componentes principales identificó las componentes que definieron los ambientes genómicos preferidos para la integración proviral en casos de PET/MAH. CONCLUSIONES: El HTLV-1 se integró con mayor frecuencia en regiones de la cromatina ricas en islas de citocina fosfato guanina (CpG), de alta densidad de genes y de repeticiones tipo LINE (elemento disperso largo [long interspersed element]) y transposones de ADN que, en conjunto, conformarían los ambientes genómicos blanco de integración. Este nuevo escenario promoverß cambios sustanciales en el campo de la salud pública y en el manejo epidemiológico de las enfermedades infecciosas, y permitirß desarrollar potentes herramientas para incrementar la eficiencia de la vigilancia epidemiológica.
OBJECTIVE: Characterize the genomic environment of the sequences adjacent to human T-cell lymphotropic virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in different regions of Colombia and Japan. METHODS: A total of 71 recombinant clones with human genome sequences adjacent to 5' LTR in patients with HAM/TSP were compared to the Genome Browser and GenBank databases. Sixteen structural and compositional genome variables were identified, and statistical analysis was conducted in the R computer program, version 2.8.1, in a 0.5 Mb window. RESULTS: A total of 43.0 percent of the proviruses were located in the group C chromosomes; 74 percent of the sequences were located in the telomeric and subtelomeric regions (P < 0.05). A cluster analysis was used to establish the hierarchical relations between the genome characteristics included in the study. The analysis of principal components identified the components that defined the preferred genome environments for proviral integration in cases of HAM/TSP. CONCLUSIONS: HTLV-1 was integrated more often in chromatin regions rich in CpG islands with a high density of genes and LINE type repetitions, and DNA transposons which, overall, would form the genomic environments targeted for integration. This new scenario will promote substantial changes in the field of public health and in epidemiological management of infectious diseases. It will also foster the development of powerful tools for increasing the efficiency of epidemiological surveillance.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Genoma Humano , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Provírus/genética , Sequências Repetidas Terminais/genética , Integração Viral/genética , Mapeamento Cromossômico , Cromossomos Humanos/genética , Colômbia/epidemiologia , Ilhas de CpG , DNA Recombinante/genética , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologia , Retroelementos/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoAssuntos
Humanos , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/virologia , DNA Viral/análise , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/transmissão , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/transmissãoRESUMO
The objective of the present study was to describe motor behavioral changes in association with histopathological and hematological findings in Wistar rats inoculated intravenously with human T-cell lymphotropic virus type 1 (HTLV-1)-infected MT2 cells. Twenty-five 4-month-old male rats were inoculated with HTLV-1-infected MT2 cells and 13 control rats were inoculated with normal human lymphocytes. The behavior of the rats was observed before and 5, 10, 15, and 20 months after inoculation during a 30-min/rat testing time for 5 consecutive days. During each of 4 periods, a subset of rats was randomly chosen to be sacrificed in order to harvest the spinal cord for histopathological analysis and to obtain blood for serological and molecular studies. Behavioral analyses of the HTLV-1-inoculated rats showed a significant decrease of climbing, walking and freezing, and an increase of scratching, sniffing, biting, licking, and resting/sleeping. Two of the 25 HTLV-1-inoculated rats (8 percent) developed spastic paraparesis as a major behavioral change. The histopathological changes were few and mild, but in some cases there was diffuse lymphocyte infiltration. The minor and major behavioral changes occurred after 10-20 months of evolution. The long-term observation of Wistar rats inoculated with HTLV-1-infected MT2 cells showed major (spastic paraparesis) and minor motor abnormalities in association with the degree of HTLV-1-induced myelopathy.
Assuntos
Animais , Humanos , Masculino , Ratos , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Paraparesia Espástica Tropical/virologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Vírus Linfotrópico T Tipo 1 Humano/genética , Reação em Cadeia da Polimerase , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/patologia , Fatores de Tempo , Carga ViralRESUMO
Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Dermatite/virologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Paraparesia Espástica Tropical/virologia , Provírus/isolamento & purificação , Dermatopatias Virais/virologia , Biomarcadores/análise , Portador Sadio , Progressão da Doença , DNA Viral/análise , Vírus Linfotrópico T Tipo 1 Humano/genética , Provírus/genética , Fatores de Risco , Carga ViralRESUMO
Background: Human T lymphotropic virus type I is associated with tropical spastic paraparesis, that is a chronic and progressive disease which damages specially the cortiespinal tracts. The pathogenesis of this degenerative process remains unknown. Aim: To identify histopathological aspects that could suggest a pathogenic hypothesis we studied immunohistochemical features in spinal cords obtained from patients that died due to progressive spastic paraparesis. Patients and Methods: Five males and five females, who died between 1990 and 2000, with a mean age of 52 years and mean disease duration of 8.6, were studied. All had a complete clinical and virological diagnosis. Samples were obtained from the frontal motor cortex and spinal cord (cervical, dorsal and lumbar segments), were fixed in formol (10 percent), included in paraffin, and stained with Haematoxylin and Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament antibodies 1:100 (M0762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700 ZYMED), anti-tau 1:100 (A0024DAKO) and anti-ubiquitine 1:50 (NCL UBIQm Novocastra). Results: All cases had demyelinization and axonal loss in the cortico-spinal tracts; distal and segmental demyelinization of Goll tract; axonal thickening, amyloid precursor protein deposits in the white matter; tau protein aggregation in the spinal cord oligodendrocytes; axonal ubiquitination of sensitive and motor tracts, and subcortical white matter. Neurona! injury was absent. Conclusions: The systematic damage of motor and sensitive tracts of the spinal-cord and the absence of neurona! damage, defines a degenerative process limited to axons. This central axonopathie could be caused by a disturbance of axoplasmic transport.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 1 Humano , Degeneração Neural/patologia , Paraparesia Espástica Tropical/patologia , Medula Espinal/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Transporte Axonal/fisiologia , Axônios/patologia , Axônios/virologia , Imuno-Histoquímica , Degeneração Neural/virologia , Paraparesia Espástica Tropical/virologia , Reação em Cadeia da Polimerase , Medula Espinal/virologia , Coloração e Rotulagem , Ubiquitina/metabolismo , Proteínas tau/metabolismoRESUMO
O presente estudo avaliou a ocorrência da infecção pelo HTLV-1 e seus subtipos em amostras de sangue de pacientes com diagnóstico clínico de paraparesia espástica tropical/mielopatia associada ao Htlv-1. A detecção da infecção pelo HTLV realizou-se através de testes sorológico e molecular. Cinco amostras estavam infectadas pelo HTLV-1 do subtipo Cosmopolita, subgrupo Transcontinental. Os resultados obtidos confirmam a ocorrência de infecção pelo HTLV-1 em pacientes com diagnóstico clínico de paraparesia espástica tropical/mielopatia associada ao Htlv-1em Belém, Pará.
The present study evaluated the occurrence of HTLV-1 and its subtypes in blood samples of patients presenting symptoms of tropical spastic paraparesis/HTLV-1 associated myelopathy. The detection of HTLV infection was performed by serological and molecular assays. Five patients were infected by HTLV-1 of the Cosmopolitan subtype, subgroup Transcontinental. The results confirm the occurrence of HTLV-1 infection among patients with clinical diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy in Belém, Pará.
Assuntos
Humanos , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/virologia , Alinhamento de Sequência , Sequência de Bases , DNA Viral , Ensaio de Imunoadsorção Enzimática , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Paraparesia Espástica Tropical/diagnósticoRESUMO
In this study, the epidemiological and clinical features observed in solely HTLV-II-infected individuals were compared to those in patients co-infected with HIV-1. A total of 380 subjects attended at the HTLV Out-Patient Clinic in the Institute of Infectious Diseases "Emilio Ribas" (IIER), São Paulo, Brazil, were evaluated every 3-6 months for the last seven years by infectious disease specialists and neurologists. Using a testing algorithm that employs the enzyme immuno assay, Western Blot and polymerase chain reaction, it was found that 201 (53 percent) were HTLV-I positive and 50 (13 percent) were infected with HTLV-II. Thirty-seven (74 percent) of the HTLV-II reactors were co-infected with HIV-1. Of the 13 (26 percent) solely HTLV-II-infected subjects, urinary tract infection was diagnosed in three (23 percent), one case of skin vasculitis (8 percent) and two cases of lumbar pain and erectile dysfunction (15 percent), but none myelopathy case was observed. Among 37 co-infected with HIV-1, four cases (10 percent) presented with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile. Two patients showed paraparesis as the initial symptom, two cases first presented with vesical and erectile disturbances, peripheral neuropathies were observed in other five patients (13 percent), and seven (19 percent) patients showed some neurological signal or symptoms, most of them with lumbar pain (five cases). The results obtained suggest that neurological manifestations may be more frequent in HTLV-II/HIV-1-infected subjects than those infected with HTLV-II only.
Neste estudo, as características epidemiológicas e clínicas observadas nos indivíduos infectados pelo HTLV-II foram comparadas com os pacientes co-infectados com HIV-1. Um total de 380 indivíduos atendidos na clínica do Ambulatório HTLV do Instituto de Infectologia "Emilio Ribas" (IIER), São Paulo, Brasil, foram avaliados a cada 3-6 meses nos últimos sete anos por especialistas em doenças infecciosas e neurologistas. Usando um algoritmo que emprega ensaio imunoenzimático, Western Blot e reação em cadeia de polimerase, foram incluídos 201 (53 por cento) pacientes infectados pelo HTLV-I e 50 (13 por cento) infectados pelo HTLV-II. Trinta e sete (74 por cento) eram co-infectados pelo HTLV-II e HIV-1. Dos 13 (26 por cento) indivíduos unicamente infectados pelo HTLV-II, infecção do trato urinário foi diagnosticada em três, um com vasculite e em dois casos dor lombar e disfunção erétil mas nenhum caso de mielopatia foi observado. Entre 37 pacientes co-infectados com HIV-1, quatro (10 por cento) casos apresentaram com paraparesia espástica tropical/mielopatia associada ao HTLV similar. Dois casos mostraram paraparesia como sintoma inicial, dois outros casos se apresentaram primeiramente com distúrbios vesical e erétil e as neuropatias periféricas foram observadas em cinco pacientes (13 por cento). Outros sete (19 por cento) pacientes mostraram algum sinal ou sintoma neurológico, a maioria deles com dor lombar (cinco casos). Os resultados sugerem que as manifestações neurológicas podem ser mais freqüentes em indivíduos co-infectados pelo HTLV-II/HIV-1 do que nos indivíduos infectados somente pelo HTLV-II.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , HIV-1 , Infecções por Deltaretrovirus/complicações , Infecções por HTLV-II/complicações , /imunologia , Paraparesia Espástica Tropical/virologia , Algoritmos , Brasil/epidemiologia , Infecções por Deltaretrovirus/epidemiologia , Infecções por HTLV-II/epidemiologia , Técnicas Imunoenzimáticas , Paraparesia Espástica Tropical/diagnóstico , Reação em Cadeia da Polimerase , Prevalência , Fatores de RiscoRESUMO
Background: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. Aim: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. Material and methods: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Results: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87 percent of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80 percent of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. Conclusions: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/patologia , Infecções por HTLV-I/patologia , Vírus Linfotrópico T Tipo 1 Humano , Imageamento por Ressonância Magnética , Paraparesia Espástica Tropical/patologia , Medula Espinal/patologia , Atrofia , Encéfalo/virologia , Diagnóstico Diferencial , Infecções por HTLV-I/virologia , Paraparesia Espástica Tropical/virologia , Medula Espinal/virologiaRESUMO
The product of human T-cell lymphotropic virus type 1 (HTLV-1) tax gene has a transactivating effect of the viral and cellular gene expression. Genetic variations in this gene have been correlated with differences in clinical outcomes. Based upon its diversity, two closely related substrains, namely tax A and tax B, have been described. The tax A substrain has been found at a higher frequency among human T-cell leukemia virus type 1 (TSP/HAM) patients than among healthy HTLV-I-infected asymptomatic subjects in Japan. In this study, we determined the distribution of tax substrains in HTLV-I-infected subjects in the city of São Paulo, Brazil. Using the ACCII restriction enzyme site, we detected only tax A substrain from 48 TSP/HAM patients and 28 healthy HTLV-I carriers. The sequenced tax genes from nine TSP/HAM patients and five asymptomatic HTLV-I carriers showed a similar pattern of mutation, which characterizes tax A. Our results indicate that HTLV-I tax subtypes have no significant influences on TSP/HAM disease progression. Furthermore, monophyletic introduction of HTLV-I to Brazil probably occurred during the African slave trade many years ago.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Mutação , Paraparesia Espástica Tropical/virologia , Produtos do Gene tax/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Variação Genética , Polimorfismo de Fragmento de RestriçãoRESUMO
To evaluate the human T-cell lymphotropic virus type I (HTLV-I) proviral DNA load among asymptomatic HTLV-I-infected carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), real time PCR using TaqMan probes for the pol gene was performed in two million peripheral blood mononuclear cells (PBMC). The albumin gene was the internal genomic control and MT2 cells were used as positive control. The results are reported as copies/10,000 PBMC, and the detection limit was 10 copies. A total of 89 subjects (44 HAM/TSP and 45 healthy HTLV-I-infected carriers) followed up at the Institute of Infectious Diseases "Emilio Ribas" and in the Neurology Division of Hospital of Clínicas were studied. The asymptomatic HTLV-I-infected carriers had a median number of 271 copies (ranging from 5 to 4756 copies), whereas the HAM/TSP cases presented a median of 679 copies (5-5360 copies) in 10,000 PBMC. Thus, HAM/TSP patients presented a significantly higher HTLV-I proviral DNA load than healthy HTLV-I carriers (P = 0.005, one-way Mann-Whitney test). As observed in other persistent infections, proviral DNA load quantification may be an important tool for monotoring HTLV-I-infected subjects. However, long-term follow-up is necessary to validate this assay in the clinical setting.
Assuntos
Humanos , DNA Viral/análise , Paraparesia Espástica Tropical/virologia , Provírus/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Estudos de Casos e Controles , DNA Viral/genética , DNA Viral/imunologia , Leucócitos Mononucleares/imunologia , Reação em Cadeia da Polimerase , Paraparesia Espástica Tropical/imunologia , Provírus/imunologia , Carga Viral , Vírus Linfotrópico T Tipo 1 Humano/imunologiaRESUMO
O Ministério da Saúde (Programa DST e Aids) reuniu especialistas para elaborar um guia informativo de manejo do paciente com HTLV. Dentre os diferentes tópicos, foram contemplados os aspectos neurológicos associados à infecção pelo HTLV. Um caso suspeito de doença neurológica associada ao HTLV deve incluir alteração de força e reflexos, parestesias distais e disfunção autonômica. A investigação do caso suspeito deve ser baseada na síndrome exibida pelo paciente. Para o paciente com síndrome medular, deve-se solicitar ressonância magnética da medula ou mielografia, assim como, estudo do líquor. Para o paciente com síndrome neuropática ou miopática, deve-se solicitar eletroneuromiografia e dosagem de CPK, e para aquele com síndrome autonômica, pesquisa de hipotensão postural, ultrassonografia das vias urinárias e estudo urodinâmico. O tratamento pode ser sintomático (espasticidade, bexiga neurogênica, constipação intestinal e dor neuropática) e específico a ser feito em centros especializados.
Assuntos
Humanos , Viroses do Sistema Nervoso Central , Infecções por Deltaretrovirus , Brasil , Viroses do Sistema Nervoso Central/diagnóstico , Viroses do Sistema Nervoso Central/terapia , Viroses do Sistema Nervoso Central/virologia , Infecções por Deltaretrovirus/diagnóstico , Infecções por Deltaretrovirus/terapia , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/terapia , Paraparesia Espástica Tropical/virologiaRESUMO
Amostras de soro e/ou líquido céfalo-raquidiano (LCR) foram obtidas de 190 pacientes com quadro de doença neurológica crônica e progressiva, com vistas à detecção de anticorpos para os vírus linfotrópicos humanos de células T dos tipos I (HTLV-I) e II (HTLV-II), durante um período de seis anos (1996 a 2001) em Belém, Pará, Brasil. O grupo compreendia ambos os sexos (homens, 52 por cento), com idades variando de 2 a 79 anos (média, 35,9 anos). Tomando-se os resultados como um todo, 15 (7,9 por cento) indivíduos, incluindo 12 (80 por cento) mulheres adultas, apresentaram anticorpos para HTLV-I/II a partir da triagem pelo procedimento imunoenzimático (ELISA). Soros de 14 desses pacientes também foram testados utilizando-se procedimento de Western blot (WB), alcançando-se freqüências de anticorpos para HTLV-I, HTLV-II e dupla reação (HTLV-I e HTLV-II) em 10 (71,4 por cento), 3 (21,4 por cento) e 1 (7,2 por cento) indivíduos, respectivamente. As freqüências anuais de positividade para HTLV-I/II variaram de 2,6 por cento (2001) a 21,7 por cento (2000), em escala crescente no período de 1998 a 2000. Em conjunto, dificuldade na deambulação (n = 5 pacientes), espasticidade (n = 4) e hipotonia crural compreenderam 80 por cento das manifestações clínicas registradas entre os 15 pacientes cujas amostras de soro continham anticorpos para HTLV-I/II, com base em ELISA. Tais resultados oferecem indicadores quanto a uma possível associação do HTLV-I e do HTLV-II à gênese das mielopatias crônicas em Belém, norte do Brasil.
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-II/diagnóstico , Doenças do Sistema Nervoso/virologia , Paraparesia Espástica Tropical/virologia , Brasil , Doença Crônica , Estudos de Coortes , Vírus Linfotrópico T Tipo 1 Humano/imunologia , /imunologiaRESUMO
El virus HTLV-I se asocia a varias patologías siendo las más relevantes la paraparesia espástica y la leucemia/linfoma de células T del adulto. No tiene tratamiento específico y se han intentado varios esquemas terapéuticos para su manejo. Se revisa la literatura presentando los trabajos más actualizados en relación a la terapia.
Assuntos
Humanos , Linfoma de Células T/epidemiologia , Linfoma de Células T/etiologia , Linfoma de Células T/tratamento farmacológico , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/virologia , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Leucemia-Linfoma de Células T do AdultoRESUMO
Partindo de dois oligonucleotídeos degenerados derivados de uma fração conservada da região pol de retrovírus conhecidos, foi pesquisada a presença de agente viral exógeno ou de uma seqüência endógena similar as retrovirais (ERV). A partir da amplificação do DNA pela técnica de PCR, foram testadas células mononucleares periféricas de 33 portadores de paraparesia crural espática de evolução crônica sem agente etiológico conhecido, produzindo um fragmento de aproximadamente 500 bp em 8 destas amostras...