RESUMO
Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Brasil/epidemiologia , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/virologia , Paraparesia Espástica Tropical/epidemiologia , Adulto , Dermatite/virologia , Dermatite/diagnósticoRESUMO
Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurological and clinical manifestations that do not meet diagnostic criteria for HAM. These conditions may later progress to HAM or constitute an intermediate clinical form: intermediate syndrome (IS), a mid-point between asymptomatic HTLV-1 carriers and those with full myelopathy. Thus, we determined the incidence of HAM cases in the HTLV-1-asymptomatic and IS patients, and the clinical/laboratory associated markers. A total of 204 HTLV-1-positive patients were included in this study, divided into two groups: Group 1, including 145 asymptomatic HTLV-1 subjects (ASY), and Group 2, including 59 patients with inflammatory clinical symptoms in more than three systems and a high proviral load (PVL). During a 60-month follow-up time, with the age ranging from 47 to 79 years, ten patients of the fifty-nine initially diagnosed as IS developed HAM (iHAM), and two patients of the initial 145 ASY developed HAM directly. Women were more prevalent in all groups. For the iHAM patients, the age ranged from 20 to 72 years, with a mean of 53 (±15 SD). Older age was associated with the development of HAM, higher PVL and IS; however, there was no any specific symptom or clinical sign, that was associated with risk for iHAM. In conclusion, IS cases could be an early phase of development of HAM. These findings show the presence of higher incidence probabilities in our cohort than previously reported.
RESUMO
A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups (n = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.
Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Humanos , Brasil/epidemiologia , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/transmissão , Feminino , Masculino , Adulto , Prevalência , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Adulto Jovem , Estudos de Coortes , Adolescente , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Família , Idoso , Doadores de Sangue/estatística & dados numéricos , Infecções por HTLV-II/epidemiologia , Infecções por HTLV-II/transmissão , SeguimentosRESUMO
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic disabling disease. However, there is a lack of an adequate and specific health measurement instrument validated and with good performance to assess their degree of physical disability. This led us to carry out this study and to evaluate the performance of Fiocruz's National Institute of Infectious Diseases (IDS) disability scale, a specific instrument for HAM/TSP. Ninety-two HAM/TSP patients participated in the study. One researcher applied the IDS, IPEC scale, Disability Status Scale (DSS), Expanded DSS (EDSS), Osame scale, Beck Depression Inventory, and the WHOQOL-BREF questionnaire. In parallel, blindly, and separately, other researchers applied the IDS. An inter-rater reliability analysis of the IDS, correlation analysis with the other scales, and depression and quality of life questionnaires were performed. The applicability of the IDS was also evaluated. The IDS showed high reliability in all scores. The inter-rater reliability test for the total IDS score was 0.94 (0.82-0.98) on its four dimensions. The scale adequately indicated the different degrees of disability, presenting a distribution similar to normal. There was a high correlation with the other scales (Spearman coefficients > 0.80, p < 0.001). The scale had good acceptance among users and a short application time. IDS for HAM/TSP was reliable, consistent, easy, and fast to use. It can be used for both prospective evaluations and clinical trials. The present study supports the IDS as a valid instrument to measure disability in patients with HAM/TSP compared to previously used scales.
Assuntos
Doenças Transmissíveis , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Paraparesia Espástica Tropical/diagnóstico , Reprodutibilidade dos Testes , Qualidade de VidaRESUMO
The impact of coronavirus disease 2019 (COVID-19) on people living with human T-cell leukemia virus type 1 (HTLV-1) is unknown. The aim of this study is to evaluate the COVID-19 risk factors and outcomes of HTLV-1-infected individuals. A retrospective study of seropositive HTLV-1 outpatients seen during the COVID-19 pandemic period (2020-2022) was conducted in a Tertiary Hospital in Rio de Janeiro, Brazil. We compared the demographic and comorbidity/risk factors in patients with COVID-19 and non-COVID-19 diagnoses. In addition, the clinical features of COVID-19 and vaccination status were also investigated in 51 HTLV-1-infected individuals. The majority (88.2%) had COVID-19 comorbidity/risk factors. Seven cases were vaccinated against COVID-19. Overall, 19 out of 51 (37.3%) individuals were diagnosed with COVID-19. We found differences only in the frequency of anxiety in both groups: 57.9% in the COVID-19 group vs. 15.6% in the non-COVID-19 (p < 0.05) group. Thirteen out of nineteen (68%) of the COVID-19 cases progressed to mild/moderate illness, one remained asymptomatic, and 26.3% progressed to severe illness. All of the individuals recovered at home, but the majority (57.9%) developed post-COVID-19 symptoms: anosmia and ageusia (31.6%), worsening anxiety (15.8%), and a feeling of pain in the legs (15.8%). The patients with post-COVID-19 conditions were unvaccinated. Our findings show that HTLV-1 did not increase the risk of lethal COVID-19 and underline the importance of promoting mental health in HTLV-1-infected individuals.
RESUMO
Human T cell lymphotropic virus (HTLV)-1-associated myelopathy is a chronic, disabling inflammatory disorder of the spinal cord caused by HTLV-1 infection. The diagnosis of HTLV-1-associated myelopathy (HAM) is based on clinical and laboratorial findings. The disease is characterized by the presence of spastic paraparesis associated with detection of anti-HTLV-1 antibodies or HTLV-1 genomes in blood and cerebrospinal fluid (CSF). New inflammatory markers have been proposed for the diagnosis and assessment of the prognosis of HAM. We reviewed the laboratory diagnostic and potential surrogate markers for HAM. The serological screening tests for detection of anti-HTLV-1/2 antibodies are highly sensitive and specific, but confirmation and typing of HTLV-1 or HTLV-2 infection by other serological or molecular methods are essential. Detection of intrathecal anti-HTLV-1 antibodies and quantification of the HTLV-1 provirus in CSF provide additional evidence for diagnosis especially in atypical cases or where alternative causes of neuroinflammation cannot be excluded. The CXC motif chemokine ligand 10 and neopterin in serum and CSF are now emerging as inflammatory markers with prognostic value and for HAM monitoring and management. In addition, measures of neurodegeneration, such as neurofilament light chain in the CSF and blood, may also contribute to the HAM prognosis. This review is useful for clinicians and researchers evaluating potential benefits and limitations of each biomarker in clinical practice. The advent of new markers makes it necessary to update the criteria for the best evidence-based approach and for worldwide consensus regarding the use of diagnostic and surrogate markers for HAM.
Assuntos
Infecções por HIV , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Infecções por HIV/complicações , Anticorpos Anti-HTLV-I , Biomarcadores , Linfócitos TRESUMO
The origin of brain white matter lesion found in HTLV-1-associated myelopathy (HAM/TSP) remains undefined. We investigated the association between white matter lesions in HAM/TSP with cardiovascular risk factors. The group of 40 patients with HAM/TSP included 60% females and mean age of 58.6 ± 8 years old. The probability of 10-year cardiovascular disease was low in 53%, moderate in 38%, and high in 10% of the patients. There was no difference between the cardiovascular risk factors in HAM/TSP patients with and without brain lesions (p > 0.05). Our data suggest that the brain white matter abnormalities are not associated to increased cardiovascular risk in HAM/TSP.
Assuntos
Doenças Cardiovasculares , Vírus Linfotrópico T Tipo 1 Humano , Doenças do Sistema Nervoso , Paraparesia Espástica Tropical , Substância Branca , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/patologia , Fatores de Risco , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
The association between high proviral load (PVL) in peripheral blood mononuclear cells (PBMC), cognitive disturbance and white matter brain lesions in HTLV-1-infected individuals is still undefined. A cross-sectional study included 62 participants: 22 asymptomatic carriers (mean age 43.4 ± 13.1 years old), 22 patients with HTLV-1-associated myelopathy (HAM/TSP) (mean age 51.5 ± 8.7 years old), and 18 uninfected controls (mean age 52.3 ± 11.1 years old). All individuals fulfilled the following criteria: between 18 and 65 years of age, more than 4 years of formal education, and completed neuropsychological evaluation and HTLV-1 serology. Infected individuals underwent brain conventional magnetic resonance imaging and PVL quantitative PCR (qPCR). Statistical analysis was adjusted in the models by age and education. Cognitive deficit was observed in all groups. Patients with HAM/TSP showed higher neurocognitive deviation in attention and motor skills, higher frequency (84%) of brain white matter lesions, and higher PVL median (range) 8.45 (0.5-71.4) copies/100 PBMC. Brain white matter lesion was associated with verbal memory deficit in HTLV-1-infected individuals (HAM/TSP and asymptomatic carriers) (p = 0.026). In addition, there was a correlation between higher PVL and neurocognitive dysfunction score (processing speed of visuomotor information and visuoconstructive praxis) in HTLV-1-infected patients. The study demonstrates an association between HTLV-1 infection, neurocognitive disorder, and white matter brain lesions on MRI as well as a correlation with higher HTLV-1 PVL, suggesting that the central nervous system involvement by HTLV-1 is not restricted to the spinal cord but involves the whole neuro-axis. HTLV-1-infected individuals should be tested for cognitive impairment.
Assuntos
Disfunção Cognitiva , Vírus Linfotrópico T Tipo 1 Humano , Substância Branca , Adulto , Encéfalo/diagnóstico por imagem , Pré-Escolar , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Leucócitos Mononucleares , Pessoa de Meia-Idade , Provírus/genética , Carga Viral , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infectious chronic-inflammatory disease, which can lead to lower limb motions. METHODS: The study evaluated the effects of serial Pilates exercises on the clinical and immunological profiles of patients with HAM/TSP. Eight patients with ages ranging from 39 to 70 years old (2 males and 6 females), 2 wheelchair users and 6 with compromised gait, were evaluated. The patients were submitted to 20 Pilates sessions for 10 weeks. Data were collected at 3 time points (beginning of the study, after Pilates sessions and after 10 weeks without Pilates) and consisted of evaluations of the pain level, spasticity, motor strength, balance, mobility, functional capacity, quality of life and quantification of IFN-γ, IL-10 and IL-9 cytokines levels. RESULTS: After the Pilates sessions, significant improvements in pain level, static and dynamic balance, trunk control, mobility and quality of life were observed, with simultaneous and significant reductions in the serum levels of the cytokines IFN-γ and IL-10. However, after 10 weeks without Pilates, there were significant changes in terms of increasing pain and regression of mobility, with no changes in strength, spasticity, functional capacity in any of the periods of the study. CONCLUSIONS: The results suggest that Pilates may be a promising auxiliary physical therapy for patients with HAM/TSP.
Assuntos
Técnicas de Exercício e de Movimento , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Adulto , Idoso , Terapia por Exercício , Feminino , Humanos , Interferon gama , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/terapia , Projetos Piloto , Qualidade de Vida , Linfócitos TRESUMO
A high proviral load (PVL) is recognized as a risk factor for human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but there is a lack of prospective studies evaluating whether or not HTLV-1 carriers with high PVL are at risk of developing HAM/TSP or other HTLV-1-related diseases. Here, we compare the incidence of clinical manifestations and the cytokine levels in 30 HTLV-1 carriers with high (> 50,000 copies/106 PBMC) and an equal number of subjects with low proviral load. Participants were followed for 3 to 16 years (median of 11 years). The PVL, IFN-γ, TNF, and IL-10 levels were quantified at entry and at the end of the follow-up. Among the self-reported symptoms in the initial evaluation, only the presence of paresthesia on the hands was more frequent in the group with high PVL (p < 0.04). The production of IFN-γ was higher in the group with high PVL group (median of 1308 versus 686 pg/ml, p < 0.011) when compared with the control group in the first assessment. There was no difference in the occurrence of urinary symptoms or erectile dysfunction, periodontal disease, Sicca syndrome, and neurologic signs between the two groups during the follow-up. The observation that none of the HTLV-1 carriers with high PVL and with exaggerated inflammatory response progressed to HAM/TSP indicates that other factors in addition to the PVL and an exaggerated immune response are involved in the pathogenesis of HAM/TSP.
Assuntos
Portador Sadio/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucócitos Mononucleares/imunologia , Provírus/imunologia , Adulto , Idoso , Portador Sadio/diagnóstico , Portador Sadio/virologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/genética , Disfunção Erétil/imunologia , Disfunção Erétil/virologia , Feminino , Expressão Gênica , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/genética , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/crescimento & desenvolvimento , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Noctúria/diagnóstico , Noctúria/genética , Noctúria/imunologia , Noctúria/virologia , Provírus/crescimento & desenvolvimento , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/virologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Carga Viral/imunologiaRESUMO
The human T-cell lymphotropic virus type 1 (HTLV-1) infects 5-10 million people worldwide and causes fatal and disabling diseases in a significant proportion of them. A chronic myelitis named HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the typical neurological manifestation of HTLV-1. However, other neurological syndromes can be either associated with HAM/TSP or occur in isolation in the HTLV-1 infected individual. Although this fact has been widely described over the years, it has been somewhat neglected by the mainstream literature, which has been largely focused on HAM/TSP. Cognitive dysfunction, encephalopathy, neurogenic bladder, motor neuron disease, inflammatory myopathies, polyneuropathy, and dysautonomia can also occur in the HTLV-1 infected patient and may remain unnoticed to the unsuspecting physician. In the present review, we intend to draw attention, primarily to the infectious disease specialist and to the general practitioner, to the fact that HTLV-1 has a broader neurological spectrum than the designation HAM/TSP suggests and that infected individuals may harbor other neurological syndromes in addition to HAM/TSP.
Assuntos
Infecções por HTLV-I/complicações , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/patologia , HumanosRESUMO
Human T-lymphotropic virus 1 (HTLV-1) was the first recognized human retrovirus. Infection can lead to two main symptomatologies: adult T-cell lymphoma/leukemia (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Each manifestation is associated with distinct characteristics, as ATLL presents as a leukemia-like disease, while HAM/TSP presents as severe inflammation in the central nervous system, leading to paraparesis. Previous studies have identified molecules associated with disease development, e.g., the downregulation of Foxp3 in Treg cells was associated with increased risk of HAM/TSP. In addition, elevated levels of CXCL10, CXCL9, and Neopterin in cerebrospinal fluid also present increased risk. However, these molecules were only associated with specific patient groups or viral strains. Furthermore, the majority of studies did not jointly compare all clinical manifestations, and robust analysis entails the inclusion of both ATLL and HAM/TSP. The low numbers of samples also pose difficulties in conducting gene expression analysis to identify specific molecular relationships. To address these limitations and increase the power of manifestation-specific gene associations, meta-analysis was performed using publicly available gene expression data. The application of supervised learning techniques identified alterations in two genes observed to act in tandem as potential biomarkers: GBP2 was associated with HAM/TSP, and CD40LG with ATLL. Together, both molecules demonstrated high sample-classification accuracy (AUC values: 0.88 and 1.0, respectively). Next, other genes with expression correlated to these genes were identified, and we attempted to relate the enriched pathways identified with the characteristic of each clinical manifestation. The present findings contribute to knowledge surrounding viral progression and suggest a potentially powerful new tool for the molecular classification of HTLV-associated diseases.
RESUMO
This narrative review, which is based on a systematic literature search following the PRISMA guidelines, provides a general overview of Human T-cell Lymphotropic Virus type 1 (HTLV-1) and associated diseases: Adult T-cell Leukaemia-Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in Latin America, focusing on epidemiology and prevention. Using the published information on HTLV-1, ATLL and HAM/TSP prevalence, we present comprehensive and accurate maps and tables, and developed an algorithm to assist in the prevention of HTLV-1 transmission through breastfeeding while considering socio-economic status. Latin America is an interesting scenario to study HTLV-1 because of the diverse origin of its population. Apart from the expected high prevalence in inhabitants of African ancestry, the presence of endemic foci affecting indigenous populations is particularly striking. ATLL prevention is the biggest challenge in this field. Most ATLL cases are transmitted through breastfeeding; thus, prevention methods to avoid ATLL in endemic countries have to be focused on this. In view of the high inequality in most Latin American countries, reduction in breastfeeding duration, freezing/thawing and pasteurisation of breastmilk can be suitable interventions in poor settings, considering that avoiding the risk of malnutrition and infant mortality must be the priority.
Cette revue narrative, qui repose sur une recherche bibliographique systématique conforme aux recommandations de PRISMA, fournit un aperçu général sur le virus lymphotropique des lymphocytes T humaines de type 1 (HTLV-1) et les maladies associées: Le lymphome leucémique des cellules T d'adulte (ATLL)) et la myélopathie/paraparésie spastique tropicale (HAM/TSP) associée à HTLV-1 en Amérique latine, en se focalisant sur l'épidémiologie et la prévention. En utilisant les informations publiées sur la prévalence de HTLV-1, ATLL et HAM/TSP, nous présentons des cartes et des tableaux complets et précis et avons développé un algorithme pour aider à la prévention de la transmission du HTLV-1 par l'allaitement tout en tenant compte du statut socioéconomique. L'Amérique latine est un scénario intéressant pour l'étude de HTLV-1 en raison de la diversité des origines de sa population. Outre la forte prévalence escomptée chez les habitants de descendance africaine, la présence de foyers endémiques affectant les populations autochtones est particulièrement frappante. La prévention de l'ATLL est le plus gros défi dans ce domaine. La plupart des cas d'ATLL sont transmis par l'allaitement. Ainsi, les méthodes de prévention pour éviter l'ATLL dans les pays d'endémie doivent être concentrées sur cela. Compte tenu de la forte inégalité qui règne dans la plupart des pays d'Amérique latine, la réduction de la durée de l'allaitement, la congélation/décongélation et la pasteurisation du lait maternel peuvent constituer des interventions appropriées dans les milieux pauvres, tout en considérant que la priorité est d'éviter les risques de malnutrition et de mortalité infantile.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Humanos , América Latina/epidemiologiaRESUMO
The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about 20 million people worldwide and causes immune-mediated diseases of the nervous system. The classical neurological presentation of HTLV-1 infection is the so-called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, HAM/ TSP is not the only neurological outcome that can result from HTLV-1 infection. In this Review it is made an update on the many aspects of this important neurological condition, the HTLV-1 neurological complex.
O vírus linfotrópico de células T humanas tipo 1 (HTLV-1) é um retrovírus que infecta cerca de 20 milhões de pessoas em todo o mundo e causa doenças imunomediadas do sistema nervoso. A apresentação neurológica clássica da infecção pelo HTLV-1 é a chamada paraparesia espástica tropical / mielopatia associada ao HTLV-1 (HAM/TSP). HAM / TSP,no entanto, não é o único desfecho neurológico que pode resultar da infecção pelo HTLV-1. Nesta revisão, é feita uma atualização sobre vários aspectos desta importante condição neurológica, o complexo neurológico do HTLV-1.
Assuntos
Humanos , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Paraparesia Espástica Tropical/etiologia , Doenças do Sistema Nervoso/diagnóstico , Corticosterona/uso terapêutico , Infecções por HTLV-I/tratamento farmacológico , Progressão da Doença , Diagnóstico Diferencial , Esclerose Lateral AmiotróficaRESUMO
We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.
Assuntos
Sistema ABO de Grupos Sanguíneos , Anticorpos Antivirais/sangue , Incompatibilidade de Grupos Sanguíneos , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Paraparesia Espástica Tropical/transmissão , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Cirrose Hepática Alcoólica/diagnóstico , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/terapia , Paraparesia Espástica Tropical/virologia , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Abstract The human T-cell lymphotropic virus-1 (HTLV-1) affects worldwide population; the estimated number of currently infected individuals is 10-20 million. In this report, we describe the clinical findings of three family members with vertical transmission of HTLV-1. This case report highlights the importance of healthcare providers who have optimal knowledge about HTLV-1 including its transmission and pertinent attributes, and who are able to provide affected individuals with adequate information regarding their condition.
Assuntos
Humanos , Feminino , Criança , Infecções por HTLV-I/transmissão , Transmissão Vertical de Doenças InfecciosasRESUMO
Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies (Abs) represents conclusive evidence of a specific immune response in the central nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a confirmatory test for HTLV-1 infection. The aim of this study was to standardise the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands of greater intensity in the CSF compared to serum (or bands in only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs were not detected in the control patients. The most frequent intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env (GD21 and rgp46-I) and gag (p24) proteins represents the most important humoral pattern in HAM/TSP. This response may be used as a diagnostic marker, considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and the pathogenesis of this neurological disease.
Assuntos
Humanos , Anticorpos Antivirais , Western Blotting/normas , Sistema Nervoso Central/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Paraparesia Espástica Tropical/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Sistema Nervoso Central/metabolismo , Ensaio de Imunoadsorção Enzimática , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/líquido cefalorraquidiano , Sensibilidade e EspecificidadeRESUMO
Fifteen families with clustering of infective dermatitis associated with HTLV-1 (IDH) and/or HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) were observed among 28 families of IDH index cases, 93% of them occurring in two generations. With the exception of two mothers of children with IDH, all the mothers with HAM/TSP had at least one child with HAM/TSP. This is the first report of such clustering involving many families.
Assuntos
Dermatite/epidemiologia , Dermatite/virologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologia , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with neoplasias and inflammatory diseases, such as adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected individuals present a spontaneous T lymphocyte proliferation. This phenomenon is related to the HTLV-1-proviral load and the persistence of the infection. Viral proteins induce many cellular mediators, which can be associated with the abnormal cellular proliferation. The intracellular levels of glutathione (GSH) are important to modulate the cellular proliferation. The aim of this study was to investigate the correlation between the modulation of intracellular GSH levels and the spontaneous lymphocyte proliferation during the HTLV-1 infection. Intracellular GSH level can be modulated by using dl-buthionine-[S,R]-sulfoximine (BSO, GSH synthesis inhibitor) and N-acetylcysteine (NAC, peptide precursor). Our results demonstrated that BSO was capable of inducing a decrease in the spontaneous proliferation of PBMC derived from HTLV-1 carriers. On the other hand, the GSH precursor induces an increase in mitogen-stimulated cellular proliferation in infected and uninfected individuals. Similar results were observed by the inhibition of ABCC1/MRP1 protein, augmenting the mitogen-induced proliferation. This effect can be related with an increase in the GSH levels since ABCC1/MRP1 transports GSH to the extracellular medium. There was a significant difference on the expression of CD69 and CD25 molecules during the lymphocyte activation. We did not observe any alterations on CD25 expression induced by BSO or NAC. However, our results demonstrated that NAC treatment induced an increase in CD69 expression on unstimulated CD8(+) T lymphocytes obtained from HTLV-1 infected individuals, healthy donors and HTLV carriers. Therefore, our results suggest that the cellular proliferation promoted by the infection with HTLV-1 and the activation phenotype of CD8(+) T lymphocytes can be regulated by changing the intracellular GSH levels; suggesting the modulation of these intracellular levels as a new approach for the treatment of pathologies associated with the HTLV-1 infection.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Portador Sadio/imunologia , Glutationa/metabolismo , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Acetilcisteína/metabolismo , Adulto , Idoso , Linfócitos T CD8-Positivos/virologia , Proliferação de Células , Células Cultivadas , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Espaço Intracelular/metabolismo , Ativação Linfocitária , Masculino , Metionina Sulfoximina/análogos & derivados , Metionina Sulfoximina/metabolismo , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (CSF) findings in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: We studied brain and cervical spinal cord on magnetic resonance imaging (MRI) and CSF examinations of 28 Brazilian HAM/TSP patients. RESULTS: The majority of patients had severe neurological incapacity with EDSS median of 6.5 (3-8). The brain MRI showed white matter lesions (75%) and atrophy (14%). The preferential brain location was periventricular. Cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. One patient had enhancement lesions on T1 cervical spinal cord MRI. Cases with spinal cord lesions had signs of acute CSF inflammation. The brain white matter lesions predominated in the patients with higher age. CONCLUSION: Our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in HAM/TSP. The brain abnormalities are not related to the clinical picture of HAM/TSP.
OBJETIVO: Analisar a associação entre aspectos clínicos, lesões de substância branca e reação inflamatória aguda no líquido cefalorraquidiano (LCR) na mielopatia associa ao HTLV-1 (HAM/TSP). MÉTODO: Foram estudadas ressonâncias magnéticas (RM) do encéfalo/medula espinhal cervical e exame do LCR de 28 pacientes com HAM/TSP. RESULTADOS: A maioria dos pacientes apresentava grave incapacidade neurológica, com EDSS 6,5 (3-8). A RM revelou lesões da substância branca (75%) com predominância periventricular e atrofia cortical (14%). Lesões desmielinizantes cervicais ocorreram em 11% dos casos e atrofia em 3,5%. Um paciente apresentou lesão cervical na T1 com captação de contraste. Sinais de inflamação aguda no LCR ocorreram em situações de lesão da medula espinhal cervical. As alterações de substância branca do encéfalo predominaram nos indivíduos com maior faixa etária. CONCLUSÃO: Nossos achados sugerem que processo inflamatório com atividade clínica na HAM/TSP está associado a lesões da medula espinhal cervical. As anormalidades da substância branca encefálicas não são relacionadas ao quadro clínico de HAM/TSP.