George Alberto da Silva Dias

Immunopathogenesis of HTLV-1-assoaciated myelopathy/tropical spastic paraparesis (HAM/TSP)

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Only a limited percentage of infected individuals develop disease in response to the virus while the majority remain asymptomatic, and HAM/TSP is the most common clinical manifestation of the virus. HAM/TSP is an inflammatory disease of the central nervous system (CNS); however, the mechanism by which HTLV-1 induces HAM/TSP is not yet clear. CD4(+) T lymphocytes are the main reservoirs of HTLV-1 in vivo and perform an important role in the immunological response to this retrovirus. This virus-host interaction may provoke changes in the immunological response, such as the enhanced production of inflammatory cytokines and the spontaneous proliferation of T CD4(+) lymphocytes, which are implicated in the pathogenesis of HAM/TSP.

HTLV-1, Immune Response and Autoimmunity

Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren’s Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.

Formation of multiple pulmonary nodules during treatment with leflunomide

Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis and can be due to the disease itself or secondary to the medications used in order to treat it. We report the case of a 60-year-old woman who had been diagnosed with rheumatoid arthritis and developed multiple pulmonary nodules during treatment with leflunomide.

Correlation between clinical symptoms and peripheral immune response in HAM/TSP

HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.

Correction: CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Perfil clínico-epidemiológico de pacientes infectados pelo HTLV-1 em Belém/Pará

ObjectiveThe clinical-epidemiological profile of patients with HTLV-1 in Belem, Para state, Brazil was investigated describing the characteristics of these patients at an outpatient service of the Clinical and Epidemiologic Laboratory of Endemic Diseases - LCEDE from the Tropical Medicine Center - NMT of the Federal University of Para - UFPA.MethodologyIt was a descriptive, cross-sectional study with data collected from the records of HTLV-1 patients from 2000 to 2012. Descriptive analysis used Epi Info 3.2.5 software.ResultsOf the 182 patients, 35.2% were male and 64.8% female, with a predominance of married individuals (47.8%), approximately 73.6% were from Belem. Among the symptomatic patients, 51% presented neurological symptoms, 21% dermatological complaints, 18% rheumatologic complaints, and 10% autonomic complaints. Among the patients with neurological symptoms, 16 (39%) were diagnosed with HAM/TSP.ConclusionThere is predominance of females, aged 40-49 years, married, with informal jobs, from Belem, with neurological sings and regular return to medical visits.

Evaluation of pelvic floor muscle contraction capacity in female volleyball athletes

1 Discente do curso de Fisioterapia da Universidade do Estado do Pará (Discente do curso de Fisioterapia da Universidade do Estado do Pará). 2 Discente do curso de Fisioterapia da Universidade do Estado do Pará (Discente do curso de Fisioterapia da Universidade do Estado do Pará). 3 (Fisioterapeuta docente da Universidade do Estado do Pará) Departamento ciencias do movimento humano. 4 Mestre em fisioterapia (Fisioterapeuta pélvico) 5 Mestre (Professor Msc da Faculdade de Fisioterapia da Universidade Estadual do Pará) 6 Universidade do Estado do Pará.

Incomplete myelopathy and human T cell lymphotropic virus type-1 (HTLV-1)

This was a cross-sectional prospective study. We performed a multivariate statistical analysis of the neurological signs and symptoms of patients infected with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate them into distinct groups and identify clinical-neurological manifestations that could differentiate the various profiles. The study was performed in the city of Belém (state of Pará), located in the Amazon region of Brazil, from 2014 to 2016. We determined muscle strength and tone, reflexes, sensations, sphincter function, gait, and the Expanded Disability Status Scale score among individuals with HTLV-I. We then used exploratory statistical methods in an attempt to find different profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The filtering of the data, performed with mixed PCA, gave rise to a streamlined database with the most informative data and suggested the formation of three statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd), AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p = 0.001). The subsequent cluster analysis confirmed the formation of three clusters. The classification and regression tree demonstrated that altered gait was the most important variable for the classification of an individual with HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized MOS. The present study was able to separate patients infected by HTLV-1 into three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical manifestations that could differentiate the various patient groups.

Coordenação motora de crianças e adolescentes portadores do vírus da imunodeficiência humana

Introducao: O virus da Imunodeficiencia Humana e um lentivirus que deprime o sistema imunologico, favorecendo o desencadeamento de deficits, incluindo no sistema motor. Esses deficits podem ser gerados atraves de efeitos adversos da terapia antirretroviral. Objetivos: Descrever o perfil da coordenacao motora de criancas e adolescentes infectadas por via vertical pelo virus da Imunodeficiencia Humana e expostas ao uso de terapias antirretrovirais. Materiais e Metodos: Estudo do tipo observacional e transversal, onde foram avaliadas 34 criancas e adolescentes matriculadas na Unidade de Referencia Materno Infantil e Adolescente do Para e distribuidas em dois grupos: 1) Grupo Controle: n=13, com sorologia negativa para o virus da imunodeficiencia humana, porem expostos a medicacao no pre, peri ou pos-natal; 2) Grupo Experimental: n=21, criancas com sorologia positiva para o HIV e exposicao prolongada as terapias antirretrovirais ha mais de 1 ano. Foi utilizada a bateria de teste Korperkoordination test fur Kinder para analise do desempenho motor. A analise estatistica foi realizada pelo software Bioestat® 5.0, considerando nivel de significância de 5%. Resultados: Identificou-se no grupo experimental deficit na coordenacao motora para tarefas de equilibrio (p=0,003) e lateralizacao (p=0,007) comprometendo a conscientizacao corporal. A analise do quociente motor global e deste com relacao a idade cronologica tambem apresentaram significância, respectivamente p=0,027 e p=0,003. Conclusao: Criancas e adolescentes infectadas por via vertical pelo virus da Imunodeficiencia Humana e expostas ao uso prolongado da terapia antirretroviral apresentaram comprometimento do desempenho motor para as tarefas de equilibrio e lateralidade.

Using the International Classification of Functioning, Disability and Health as a tool for analysis of the effect of physical therapy on spasticity in HAM/TSP patients

INTRODUCTION This study aimed to evaluate spasticity in human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients before and after physical therapy using the International Classification of Functioning, Disability and Health (ICF). METHODS Nine subjects underwent physical therapy. Spasticity was evaluated using the Modified Ashworth Scale. The obtained scores were converted into ICF body functions scores. RESULTS The majority of subjects had a high degree of spasticity in the quadriceps muscles. According to the ICF codes, the spasticity decreased after 20 sessions of physical therapy. CONCLUSIONS The ICF was effective in evaluating spasticity in HAM/TSP patients.