Atuação de um programa de extensão em uma comunidade periférica na região nordeste do Brasil / Performance of an extension program in a peripheral community in the northeast region of Brazil / Realización de un programa de extensión en una comunidad periférica de la región noreste de Brasil

Objetivo: Inquérito coproscópico para reavaliar na população do estudo a frequência de parasitos intestinais identificados numa primeira etapa e investigar mudanças nos fatores de risco, adesão ao tratamento e às ações de prevenção e controle de enteroparasitoses. Método:Realização de exames coproscópicos e aplicação de um formulário estruturado para determinar a prevalência de enteroparasitoses e o perfil socioeconômico e sanitário da população de três microáreas do bairro Mangabeira na cidade de Feira de Santana, Bahia. Resultados:Em 2013 (primeiro período do estudo) a prevalência de enteroparasitos foi de 44,3% com maior frequência para Ascaris lumbricoides(32,3%), Trichuris trichiura(25,8%), Schistosoma mansoni(9,7%) e Giardia intestinalis(9,7%). No segundo período (2016) observou-se aumento da frequência do S. mansoni(19,3%) e G. intestinalis(16,1%), além do diagnóstico de Entamoeba histolytica/dispar(3,2%) não identificadas no inquérito anterior. Não foram observadas alterações das variáveis socioeconômicas e sanitárias na população reavaliada. Atividades educativas foram realizadas levando em consideração o perfil epidemiológico da população. Os portadores positivos foram encaminhados para tratamento, porém as taxas de curas foram baixas. Conclusão:Observou-se a necessidade de intensificação da promoção das ações de educação em saúde de forma continuada, associada à melhoria das condições sanitáriase ambientais da comunidade.

Objective: Coproscopic survey to reassess in study population the frequency of intestinal parasites identified in a first stage and investigate changes in risk factors, adherence to treatment and prevention and control for enteroparasitosis Method:Carrying out coproscopic exams and applying a structured form to determine the prevalence of enteroparasitosis and the socioeconomic and health profile of the population of three micro-areas of the Mangabeira neighborhood in city of Feira de Santana, Bahia. Results:In 2013 (first period) the prevalence of enteroparasites was 44.3%, with a higher frequency for Ascaris lumbricoides (32.3%), Trichuris trichiura (25.8%), Schistosoma mansoni (9.7%) and Giardia intestinalis (9.7%). In the second period (2016), an increase in the frequency of S. mansoni (19.3%) and G. intestinalis (16.1%) was observed, in addition to the diagnosis of Entamoeba histolytica/dispar (3.2%) not identified in the previous survey. No changes were observed in socioeconomic and health variables in the reevaluated population. Educational activities were carried out considering the epidemiological profile of the population. Positive carriers were referred for treatment, but cure rates were low. Conclusion:There was a need to intensify the promotion of health education actions on an ongoing basis, associated with improving the sanitary and environmental conditions of the community.

Objetivo: Encuesta coproscópica para reevaluar la población de estudio la frecuencia de parásitos intestinales identificados en una primera etapa e investigar cambios en los factores de riesgo, adherencia al tratamiento y acciones de prevención y control de enteroparasitosis. Método:Realización de exámenes coproscópicos y aplicación de un formulario estructurado para determinar la prevalencia de enteroparasitosis y el perfil socioeconómico y de salud de la población de tres microáreas del barrio Mangabeira de la ciudad de Feira de Santana, Bahía. Resultados:En 2013 la prevalencia de enteroparásitos fue 44,3%, con mayor frecuencia para Ascaris lumbricoides (32,3%), Trichuris trichiura (25,8%), Schistosoma mansoni (9,7%) y Giardia intestinalis (9,7%). En el segundo período se observó un aumento en la frecuencia de S. mansoni (19,3%) y G. intestinalis (16,1%), además Entamoeba histolytica/dispar (3,2%) no identificado en la encuesta anterior. No se observaron cambios en las variables socioeconómicas y de salud en la población reevaluada. Las actividades educativas se realizaron teniendo en cuenta el perfil epidemiológico de la población. Los portadores positivos fueron remitidos para tratamiento, pero las tasas de curación fueron bajas. Conclusión:Necesario intensificar la promoción de acciones de educación en salud de manera continua, asociadas al mejoramiento de las condiciones sanitarias y ambientales de la comunidad.

Micro duelo: adaptação do jogo Yu-Gi-Oh para o ensino da Microbiologia / Micro duel: adaptation of the game Yu-Gi-Oh for teaching Microbiology / Micro duelo: adaptación del juego Yu-Gi-Oh para la enseñanza de Microbiología

Objetivo: Relatar a experiência de professores tutores e professores da Educação Básica, participantes do curso EAD Ensino de Ciências para a Promoção de Saúde na Escola Básica, na construção de um material didático-pedagógico para ser utilizado em sala de aula. Método: Para diversificar a rotina de aulas no ensino de Ciências e Biologia, direcionadas para alunos do ensino médio, os professores da Educação Básica que trabalharam os conteúdos do módulo de Saúde e Educação, desenvolveram um jogo de cartas que aborda a microbiologia, inspirado em Yu-Gi-Oh, uma série animada de mangá (histórias japonesas em quadrinhos), onde os jogadores usam cartas para duelar, em uma batalha simulada. Resultados: O material didático descreve os principais conceitos utilizados nojogo (duelo, pontos de vida, tipos de cartas etc.), as fases do duelo e os passos para iniciar o jogo. As cartas foram adaptadas para os assuntos abordados na microbiologia e continham nome do agente, tipo, descrição, atributo em cores, nível de ação em estrelas, número da carta e os pontos de ataque e de defesa. Conclusão: Espera-se estimular a interação e o aprendizado dos estudantes, através da aquisição de habilidades indispensáveis ao desenvolvimento intelectual e facilitação dos conceitos relacionados à microbiologia.

Objective: Report the experience of tutors and Basic Education teachers, participants in the EAD course Teaching Science for Health Promotion in Basic Schools, in the construction of didactic-pedagogical material to be used in the classroom. Method: To diversify the routine of teaching Science and Biology classes, aimed at high school students, the Basic Education teachers who worked on the contents of the Health and Education module, developed a card game that addresses microbiology, inspired by Yu-Gi-Oh, an animated manga series (Japanese comic books), where players use cards to duel in a simulated battle. Results: The teaching material describes the main concepts used in the game (duel, life points, types of cards, etc.), the phases of the duel and the steps to start the game. The cards were adapted to the subjects covered in microbiology and contained the agent's name, type, description, attribute in colors, action level in stars, card number and attack and defense points. Conclusion: It is expected to stimulate student interaction and learning, through the acquisition of skills essential for intellectual development and facilitation of concepts related to microbiology.

Objetivo: Reportar la experiencia de tutores y docentes de Educación Básica, participantes del curso EADEnseñanza de Ciencias para la Promoción de la Salud en Escuelas Básicas, en la construcción de material didáctico-pedagógico para ser utilizado en aula. Método: Para diversificar la rutina de enseñanza de las clases de Ciencias y Biología, dirigidas a estudiantes de secundaria, los docentes de Educación Básica que trabajaron los contenidos Salud y Educación desarrollaron un juego de cartas que aborda la microbiología, inspirado en Yu-Gi-Oh, una serie animada de manga (cómics japoneses), donde los jugadores usan cartas para batirse en duelo en una batalla simulada. Resultados: El material didáctico describe los principales conceptos utilizados en el juego (duelo, puntos de vida, tipos de cartas, etc.), las fases del duelo y los pasos para iniciar el juego. Las tarjetas estaban adaptadas a los temas tratados en microbiología y contenían el nombre del agente, tipo, descripción, atributo en colores, nivel de acción en estrellas, número de tarjeta y puntos de ataque y defensa. Conclusión: Se espera estimular la interacción y el aprendizaje de los estudiantes, a través de la adquisición de habilidades esenciales para el desarrollo intelectual y la facilitación de conceptos relacionados con la microbiología.

TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals.

HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the in vitro neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.

Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection.

INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS: We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS: No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS: Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.

The Role of NK Cells in the Control of Viral Infection in HTLV-1 Carriers.

The cytotoxic activities of CD8+ T cells have been considered the main defense mechanism against the human T lymphotropic virus type 1 (HTLV-1). As with CD8+ T cells, NK cells can perform cytotoxic degranulation with production of cytotoxic mediators, such as perforins and granzymes. NK cells are also responsible for antibody-dependent cellular cytotoxicity (ADCC) against infected cells, but few studies have evaluated the role of NK cells in HTLV-1 infection. The aim of this study was to characterize the subsets and measure the frequency of NK cells in HTLV-1 carriers (HC) and in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and correlate these findings with the proviral load and development of HAM/TSP. The diagnosis of HTLV-1 infection was performed with a detection antibody against viral antigens by ELISA and confirmed by Western blot. Phenotypic characterization of NK cells was performed by flow cytometry. The frequencies of CD56+, CD56+CD3-, CD56+CD16+, and CD56dim cells were decreased in HAM/TSP patients. The frequency of CD56+CD3- cells was inversely correlated with proviral load in HC but not in HAM/TSP patients. HAM/TSP patients showed decreased frequency of CD56+ and CD56dim cells expressing CD16, the main receptor for ADCC. These data indicate that NK cells may play a key role in the control of HTLV-1 infection by preventing the progression of HC to HAM/TSP.

Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection

Abstract INTRODUCTION Human T-cell lymphotropic virus type 1 (HTLV-1)-associated inflammatory diseases are not well understood; however, their clinical manifestations may be influenced by the host genetic background. METHODS We genotyped 298 individuals with HTLV-1 and 380 controls for interleukin-10 (IL10) gene variants-rs3024496, rs1800871, rs1800896-and used logistic regression analysis to determine their association with clinical phenotypes. RESULTS No association with HTLV-1 infection was observed. However, allele A of rs1800896 (1082bp upstream) was associated with protection against neurological impairment, specifically overactive bladder (OR=0.447, 95% CI 0.28-0.70, p=0.001). CONCLUSIONS Our data suggests that IL10 regulation ameliorates neurological damage in HTLV-1 infections.

Local and systemic production of proinflammatory chemokines in the pathogenesis of HAM/TSP.

BACKGROUND: HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is related with high proviral load, high proinflammatory cytokine levels, and passage of infected cell from the blood to the central nervous system. We aimed to evaluate the participation of chemokines and adhesion molecules in HAM/TSP pathogenesis. METHODS: CXCL9, CXCL10, sICAM-1, and sVCAM-1 were determined by ELISA in serum and cerebrospinal fluid (CSF) of HTLV-1 infected individuals. The frequency and median fluorescence intensity (MFI) of lymphocytes and monocytes expressing ligands of adhesion molecules (CD11a and CD49d) and a chemokine receptor (CXCR3) were analyzed by flow cytometry. RESULTS: The levels of CXCL9 and CXCL10 in serum of definite HAM/TSP were higher than in serum of probable HAM/TSP and HTLV-1 carriers. Considering the production of chemokines by patients with definite HAM/TSP, CXCL9 levels were higher in serum than in CSF, and CXCL10 production was higher in CSF than in serum. Levels of adhesion molecules in serum and CSF of HTLV-1 infected individuals did not differ. The MFI of CD11a on CD4+, CD8+ and CD14+ cells was lower in definite HAM/TSP than in HTLV-1 carriers and did not differ from probable HAM/TSP and healthy subjects (HS). The frequency of lymphocytes expressing CXCR3 was lower in definite HAM/TSP than in cells of probable HAM/TSP and did not differ from carrier and HS. CONCLUSION: These data point to the participation of proinflammatory chemokines, especially CXCL10, in the pathogenesis of definite HAM/TSP.

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

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.

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.

Impaired TNF, IL-1ß, and IL-17 production and increased susceptibility to Mycobacterium tuberculosis infection in HTLV-1 infected individuals.

IFN-γ and TNF play critical roles in the control of Mycobacterium tuberculosis infection. Despite leading to an exaggerated production of inflammatory cytokines, HTLV-1 infection increases the risk of developing tuberculosis (TB). However, the immune mechanisms accounting for this phenomenon are still unclear. The aim of this study was to evaluate immunological aspects of the HTLV-1/M. tuberculosis co-infection. In this cross-sectional study, the levels of TNF, IL-1ß, and IL-17 were determined by ELISA in the supernatants of either unstimulated or tuberculin purified protein derivative (PPD) stimulated peripheral blood mononuclear cells. Cells from HTLV-1 infected individuals produced lower levels of TNF following PPD stimulation compared to unstimulated cells. IL-1ß and IL-17 production by cells from HTLV-1/M. tuberculosis co-infected individuals was lower than in cells from patients with TB. Impairment in TNF, IL-1ß, and IL-17 production upon stimulation with mycobacterial antigens may contribute to the increased susceptibility to M. tuberculosis infection observed in HTLV-1 infected individuals.

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder

ABSTRACT Aim: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL). Methods: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS) and King's Health Questionnaire. Results: The mean (SD) of the age was 52 + 14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12) on day 30 and to 03 (0-14) on day 90 (p < 0.0001). There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. Conclusion: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder.

Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of life in patients with human T cell lymphotropic virus type 1 associated overactive bladder.

AIM: To evaluate the efficacy of the onabotulinum toxin type A in the treatment of HTLV-1 associated overactive bladder and its impact on quality of life (QoL). METHODS: Case series with 10 patients with overactive bladder refractory to conservative treatment with anticholinergic or physical therapy. They received 200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive bladder symptoms score (OABSS) and King's Health Questionnaire. RESULTS: The mean (SD) of the age was 52+14.5 years and 60% were female. All of them had confirmed detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12) on day 30 and to 03 (0-14) on day 90 (p<0.0001). There was a significant improvement in 8 of the 9 domains of the King's Health Questionnaire after the intervention. Hematuria, urinary retention and urinary infection were the complications observed in 3 out of 10 patients. The mean time to request retreatment was 465 days. CONCLUSION: Onabotulinum toxin type A intravesically reduced the OABSS with last long effect and improved the quality of life of HTLV-1 infected patients with severe overactive bladder.

Association of Tuberculosis Status with Neurologic Disease and Immune Response in HTLV-1 Infection.

The human T cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 infected individuals have increased susceptibility to Mycobacterium tuberculosis infection but the influence of tuberculosis (TB) on the course of HTLV-1 infection is unknown. The aim of this study was to evaluate the influence of TB on immunological, virologic, and neurologic features of HTLV-1 infection. This is a retrospective analysis of individuals enrolled in a cohort study from an HTLV-1 clinic who were evaluated for past or latent tuberculosis (LTB) and classified clinically as HTLV-1 carriers, probable HAM/TSP and definite HAM/TSP. Spontaneous cytokine production (interferon-gamma [IFN-γ], tumor necrosis factor [TNF], and interleukin[IL]-10), serum chemokines (CXCL9 and CXCL10) and HTLV-1 proviral load were evaluated. Of 172 participants, 64 did not have histories of TB (TB- group), 81 had LTB and 27 had TB in the past (TB+ group). In the TB+ group, there was a higher frequency of HAM/TSP patients (35%) than in HTLV-1 carriers (10%) (OR = 3.8, p = .0001). HAM/TSP patients with histories of TB had higher IFN-γ/IL-10 and TNF/IL-10 ratios when compared with HAM/TSP patients without histories of TB. There were no differences in serum chemokine production and proviral load across TB groups stratified on HTLV-1 clinical status. In conclusion, TB may influence the development of HAM/TSP, and patients with these two diseases have an impairment in the modulation of immune response.

Schistosoma antigens downregulate CXCL9 production by PBMC of HTLV-1-infected individuals.

HTLV-1 is the causal agent of Adult T cell Leukemia/lymphoma (ATLL) and HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The immune response to HTLV-1-infection is polarized to the Th1-type, and the presence of CXCL9/CXCL10 chemokines may lead to an increase in the recruitment of pro-inflammatory molecules in spinal cord tissue, contributing to the damage observed in the development of HAM/TSP. It has been observed that in chronic helminth-infections, such as schistosomiasis, there is a deviation toward the Th2/regulatory immune response. OBJECTIVE: To evaluate the ability of Schistosoma spp. proteins to decrease the in vitro CXCL9 and CXCL10 production by PBMC of HTLV-1-infected individuals. METHODS: The Schistosoma proteins rSm29, rSh-TSP-2 and PIII were added to PBMC cultures of HTLV-1-infected individuals and the levels of chemokines in the supernatants were measured using a sandwich ELISA method. RESULTS: The addition of rSm29 to the cultures resulted in decreased production of CXCL9 in all the analyzed individuals and HAM/TSP group (18167±9727pg/mL, p=0.044; 20237±6023pg/mL, p=0.028, respectively) compared to the levels in unstimulated cultures (19745±9729pg/mL; 25078±2392pg/mL, respectively). The addition of rSh-TSP-2 decreased the production of CXCL9 in all studied individuals and carriers group (16136±9233pg/mL, p=0.031; 13977±8857pg/mL, p=0.026) vs unstimulated cultures (19745±9729pg/mL; 18121±10508pg/mL, respectively). Addition of PIII did not alter the results. There was no significant change in the levels of CXCL10 by the addition of the studied proteins. CONCLUSION: The Schistosoma proteins used in this study were able to down modulate the production of CXCL9, a chemokine associated with the inflammatory process in HTLV-1-infection.

Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid.

T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-γ, TNF-α and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination.

Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection.

The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10) were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7%) had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA) and antigen B (SSB) were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P < 0.05) than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.

Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)-Infected Individuals Without HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), observed in up to 5% of infected individuals. Despite low prevalence, many HTLV-1-infected patients who do not fulfill criteria for HAM/TSP present with neurological complaints related to sensory, motor, urinary, or autonomic manifestations. The aim of this study was to determine the incidence of neurologic manifestations and risk factors associated with these outcomes. METHODS: The incidence of HAM/TSP and new signs and neurologic symptoms were computed in a group of patients enrolled in a cohort study. RESULTS: Of 414 subjects, 76 had definite HAM/TSP, 87 had possible or probable HAM/TSP, and 251 subjects had no neurologic manifestation and were selected for analysis. Definite HAM/TSP developed in 5 (1.47%) patients. Follow-up of at least 3 years was achieved in 51% of patients. The incidence rate was computed in 1000 person-years (206 for hand numbness, 187 for feet numbness, 130 for nocturia, and 127 for urgency). Average incidence rate in neurological exam was 76 for leg hyperreflexia, 53 for leg weakness, and 37 for Babinski sign. In the applied Expanded Disability Status Scale, the incidence rate of worsening 1 point was 134 per 1000 person-years. Kaplan-Meier curves stratified by sex and proviral load showed that females and patients with proviral load >50,000 copies/10(6) peripheral blood mononuclear cells had a higher risk of progression. CONCLUSIONS: Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.

Functional activity of monocytes and macrophages in HTLV-1 infected subjects.

The Human T lymphotropic virus type-1 (HTLV-1) infects predominantly T cells, inducing proliferation and lymphocyte activation. Additionally, HTLV-1 infected subjects are more susceptible to other infections caused by other intracellular agents. Monocytes/macrophages are important cells in the defense against intracellular pathogens. Our aims were to determine the frequency of monocytes subsets, expression of co-stimulatory molecules in these cells and to evaluate microbicidal ability and cytokine and chemokine production by macrophages from HTLV-1 infected subjects. Participants were 23 HTLV-1 carriers (HC), 22 HAM/TSP patients and 22 healthy subjects (HS) not infected with HTLV-1. The frequencies of monocyte subsets and expression of co-stimulatory molecules were determined by flow cytometry. Macrophages were infected with L. braziliensis or stimulated with LPS. Microbicidal activity of macrophages was determined by optic microscopy. Cytokines/chemokines from macrophage supernatants were measured by ELISA. HAM/TSP patients showed an increase frequency of intermediate monocytes, but expression of co-stimulatory molecules was similar between the groups. Macrophages from HTLV-1 infected individuals were infected with L. braziliensis at the same ratio than macrophages from HS, and all the groups had the same ability to kill Leishmania parasites. However, macrophages from HTLV-1 infected subjects produced more CXCL9 and CCL5, and less IL-10 than cells from HS. While there was no correlation between IFN-γ and cytokine/chemokine production by macrophages, there was a correlation between proviral load and TNF and CXCL10. These data showed a dissociation between the inflammatory response and microbicidal ability of macrophages from HTLV-1 infected subjects. While macrophages ability to kill an intracellular pathogen did not differ among HTLV-1 infected subjects, these cells secreted high amount of chemokines even in unstimulated cultures. Moreover the increasing inflammatory activity of macrophages was similar in HAM/TSP patients and HC and it was related to HTLV-1 proviral load rather than the high IFN-γ production observed in these subjects.

Soluble IL-2 receptor and beta-2 microglobulin as possible serologic markers of neurologic disease in HTLV-1 infection.

The human T-cell leukemia virus (HTLV-1) is the causative agent of a variety of neurologic diseases, including HTLV-1 Associated Myelopathy (HAM/TSP) and overactive bladder. Investigation of immune markers such as soluble interleukin-2 receptor (sIL-2R) and beta-2 microglobulin (B2M) has shown some promising results in distinguishing patients with neurologic disease from those with carrier status. The objective of the present study was to determine if plasma levels of sIL-2R and B2M are markers of neurologic disease in individuals infected with HTLV-1. The present study was divided into two parts. A cross-sectional study and a nested case control study. In the cross-sectional study, HAM/TSP patients had higher plasma levels of B2M and sIL-2R than patients with overactive bladder and HTLV-1 carriers (P < 0.01 for all comparisons). For the nested case control study, the sIL-2 receptor test was able to distinguish patients with HAM/TSP from patients in the combined group of carriers and patients with overactive bladder with a sensitivity of 75.8% and false positive rate of 25.4%. Plasma levels of these markers did not change with the development of HAM/TSP and overactive bladder in HTLV-1 carrier patients. The present study has shown the importance of sIL-2 receptor in helping identifying HAM/TSP. However, the levels of these makers did not change significantly with the development of neurologic disease.

Treatment of strongyloidiasis in HTLV-1 and Strongyloides stercoralis coinfected patients is associated with increased TNFα and decreased soluble IL2 receptor levels.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection has been associated with recurrent and disseminated strongyloidiasis and adult T cell leukemia/lymphoma (ATLL). METHODS: We compared immunological aspects and markers for ATLL in HTLV-1 patients with or without strongyloidiasis, and evaluated the influence of Strongyloides stercoralis treatment on the immune response and clinical outcomes of HTLV-1 infection. RESULTS: Levels of TNFα and IFNγ were lower in patients coinfected with HTLV-1 and S. stercoralis than in patients with HTLV-1 only (p < 0.05), and there was an increase in TNFα levels after anthelmintic treatment. Levels of sIL-2R were higher in patients with HTLV-1 coinfected with S. stercoralis and anthelmintic treatment decreased sIL-2R levels (p < 0.05). The one patient who developed ATLL was coinfected with S. stercoralis. CONCLUSION: These data show that helminthic infection has a modulatory role in HTLV-1 infection and that S. stercoralis may be a cofactor in the development of ATLL.