Distribución geográfica y tipo de infección del virus linfotrópico T humano en pacientes peruanos 2019-2021 / Geographic distribution and type of human T-lymphotropic virus (HTLV) infection in Peruvian patients 2019-2021

En el presente estudio describimos y caracterizamos la distribución geográfica de los casos positivos confirmados a HTLV-1 y 2 de pacientes peruanos con diagnóstico presuntivo entre 2019 y 2021. De un total de 555 muestras positivas confirmadas, 546 (98,4%) fueron HTLV-1 y 9 (1,6%) HTLV-2. Además, 22 de 24 departamentos del Perú presentaron casos de HTLV-1, siendo los principales motivos de solicitud de confirmación diagnóstica: aspirante a donar sangre con prueba de tamizaje reactivo, sospecha de leucemia/linfoma y paraparesia espástica tropical. Los resultados reflejan que la identificación de los puntos críticos constituye una brecha persistente respecto al diagnóstico, siendo cruciales para reducir el número de nuevos casos en Perú.

In the present study we describe and characterize the geographic distribution of HTLV-1 and 2 positive cases from Peruvian patients with presumptive diagnosis 2019 - 2021. Of a total of 555 confirmed positive samples, 546 (98.4%) were HTLV-1 and 9 (1.6%) HTLV-2. In addition, 22 of 24 departments of Peru presented cases of HTLV-1. The main reasons for requesting a confirmatory diagnosis being: aspiring to donate blood with a reactive screening test, suspicion of leukemia/ lymphoma and tropical spastic paraparesis. The results reflect that the identification of critical points constitutes a persistent gap regarding the diagnosis, being crucial to reduce the number of new cases in Peru.

Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skills / Idosos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1apresentam comprometimento precoce em habilidades cognitivas

Abstract Background Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1 )-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1. Objective To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years. Methods This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests. Results Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group. Conclusions Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.

Resumo Antecedentes Alterações cerebrais ocorrem em indivíduos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1 (HTLV-1) (HAM) e parecem predominar em áreas subcorticais. Pouco se sabe sobre o declínio cognitivo em idosos vivendo com HTLV-1. Objetivo Avaliar o envelhecimento cognitivo de indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos. Métodos Trata-se de um estudo transversal com ex-doadores de sangue infectados pelo HTLV-1 acompanhados na coorte do Grupo Interdisciplinar de Pesquisa em HTLV-1 há 20 anos. Os grupos de estudo foram compostos por 79 indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos, sendo que 41 apresentavam HAM e 38 eram portadores assintomáticos, e 59 indivíduos soronegativos (controles) com idade ≥ 60 anos. Todos foram submetidos ao teste eletrofisiológico P300 e testes neuropsicológicos. Resultados Indivíduos com HAM apresentaram atraso na latência do P300 em relação aos demais grupos, e esse atraso de latência aumentou progressivamente com o envelhecimento. O desempenho desse grupo nos testes neuropsicológicos também foi o pior. O desempenho do grupo HTLV-1- assintomático foi semelhante ao do grupo controle. Conclusão Indivíduos com HAM apresentaram declínio cognitivo que progrediu com o envelhecimento e, embora os portadores assintomáticos do HTLV-1 pareçam apresentar envelhecimento cognitivo semelhante ao dos idosos saudáveis, justificase a preocupação com um comprometimento cognitivo subclínico nessa população.

Impaired flexibility in patients with tropical spastic paraparesis/HTLV-associated myelopathy: evaluation via pendulum fleximeter / Flexibilidade prejudicada em pacientes com paraparesia espástica tropical/mielopatia associada ao HTLV: avaliação via flexímetro pendular

Abstract Background Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility. Objective To evaluate the differences in flexibility between HTLV-1-infected individuals with and without myelopathy compared with uninfected controls. We also investigated whether age, sex, body mass index (BMI), physical activity level, or lower back pain influence flexibility in HTLV-1-infected individuals. Methods The sample consisted of 56 adults, of which 15 did not have HTLV-1, 15 had HTLV-1 without myelopathy, and 26 had TSP/HAM. Their flexibility was assessed using the sit-and-reach test and a pendulum fleximeter. Results No differences in flexibility were observed between the groups with and without myelopathy and controls without HTLV-1 infection using the sit-and-reach test. The pendulum fleximeter results of individuals with TSP/HAM presented the lowest flexibility among the groups with respect to trunk flexion, hip flexion and extension, knee flexion, and ankle dorsiflexion, even after adjusting for age, sex, BMI, level of physical activity, and lower back pain using multiple linear regression models. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced flexibility in movements: knee flexion, dorsiflexion, and ankle plantar flexion. Conclusions Individuals with TSP/HAM demonstrated reduced flexibility in most of the movements evaluated by the pendulum fleximeter. Additionally, HTLV-1-infected individuals without myelopathy demonstrated reduced knee and ankle flexibility, potentially representing a marker of myelopathic development.

Resumo Antecedentes A flexibilidade é fundamental para a execução harmoniosa dos movimentos articulares. Embora a disfunção do músculo esquelético em pacientes com HTLV-1 possa interferir na mobilidade, não está claro se esses pacientes apresentam flexibilidade reduzida. Objetivo Avaliar as diferenças de flexibilidade entre os indivíduos infectados com e sem mielopatia e o grupo controle sem infecção HTLV-1. Também investigamos se idade, sexo, índice de massa corporal (IMC), nível de atividade física ou dor lombar influenciam a flexibilidade em indivíduos infectados pelo HTLV-1. Métodos A amostra foi composta por 56 adultos, dos quais 15 não possuíam HTLV-1, 15 possuíam HTLV-1 sem mielopatia e 26 possuíam TSP/HAM. A flexibilidade foi avaliada por meio do teste de sentar e alcançar e do flexímetro de pêndulo. Resultados Não foram observadas diferenças na flexibilidade entre os grupos com e sem mielopatia no teste de sentar e alcançar. Os resultados do flexímetro pendular dos indivíduos com TSP/HAM apresentaram a menor flexibilidade entre os grupos em relação à flexão do tronco, flexão e extensão do quadril, flexão do joelho e dorsiflexão do tornozelo, mesmo após ajuste para idade, sexo, IMC, nível de atividade física e dor lombar usando modelos de regressão múltipla linear. Além disso, os indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade nos movimentos de flexão do joelho, dorsiflexão e flexão plantar do tornozelo. Conclusão Indivíduos com TSP/HAM demonstraram redução da flexibilidade na maioria dos movimentos avaliados pelo flexímetro pendular. Além disso, indivíduos infectados pelo HTLV-1 sem mielopatia demonstraram redução da flexibilidade do joelho e tornozelo, representando potencialmente um marcador de desenvolvimento mielopático.

Work ability and associated factors in people living with human T-cell leukemia virus type 1

ABSTRACT Background: Infection with the human T-lymphotropic virus type 1 (HTLV-1) affects an estimated 10-15 million people worldwide. However, knowledge of the impact of HTLV-1 infection on work ability is lacking. This study aimed to measure the frequency and identify factors associated with poor work ability in patients living with HTLV-1. Methods: This cross-sectional study included 207 individuals infected with HTLV-1 who attended the University Hospital in Salvador, Bahia, Brazil. HTLV-1 antibodies were detected in the participants' blood by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blotting. Participants answered a questionnaire on sociodemographic data, personal habits, clinical data, health-related quality of life, and work ability, evaluated using the work ability index questionnaire. A Poisson regression model with a robust variance estimate was used to identify the factors associated with the prevalence of poor work ability. Results: Patients mean age was 55.2, ranging from 19 to 84 years, 73.0% were females, 100% had monthly family income less than US$ 394, and 33.8% presented HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). No individual was classified as having excellent work ability. Poor work ability prevalence was strongly associated (prevalence ratio; 95% confidence interval [CI]) with sedentarism (1.30; 1.03-1.65), neurological symptoms (1.25; 1.02-1.52), and low physical (0.95; 0.94-0.96) and mental (0.98; 0.97-0.99) component summaries of health-related quality of life. Conclusions: Poor work ability among people living with HTLV-1 is associated with sedentarism, neurologic symptoms, and low health-related quality of life.

Silencioso e negligenciado: o que se sabe após quatro décadas do descobrimento do HTLV-1? / Silent and neglected: what is known after four decades of the discovery of the HTLV-1? / Silencioso y descuidado: ¿qué se sabe después de cuatro décadas del descubrimiento del HTLV-1?

O vírus linfotrópico T humano tipo 1 (HTLV-1) foi o primeiro retrovírus humano descoberto, descrito pela primeira vez há 41 anos. Esse retrovírus está associado ao desenvolvimento de duas doenças graves: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). Este trabalho teve como objetivo analisar as atualizações sobre o HTLV-1, destacando os aspectos clínicos, os avanços e as limitações no tratamento e na prevenção da infecção pelo HTLV-1. Para isso, foi realizada uma revisão integrativa, por meio de coleta de dados nas plataformas PubMed, LILACS e SciELO, entre março e abril de 2021. Foram incluídos 61 artigos de diferentes países. O Brasil foi o país com maior número de publicações na área: 12. Os resultados obtidos mostram que existem avanços importantes no que diz respeito ao tratamento e à prevenção da infecção pelo HTLV-1. No entanto, a falta de estudos específicos sobre o vírus, que abordem os aspectos clínicos da infecção, foi um fator limitante para este estudo, o que reforça a necessidade de investimento em novas pesquisas sobre o tema.

The Human T-lymphotropic Virus 1 (HTLV-1) was the first human retrovirus discovered, described for the first time 41 years ago. This retrovirus is associated with the development of two serious diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (HAM/TSP). This study aimed to analyze the updates about HTLV-1, highlighting the clinical aspects, advances, and limitations in the treatment and prevention of HTVL-1 infection. To this end, an integrative review was carried out, with data collection on PubMed, LILACS, and SciELO platforms, between March and April 2021. A total of 61 articles from different countries were included. Brazil was the country with the largest number of publications in the area: 12. The results showed effective advances regarding treating and preventing HTLV-1 infection. However, the lack of specific studies about the virus, which address the clinical aspects of the infection, was a limiting factor for this study, which reinforces the need for investment in new research about this topic.

El virus linfotrópico T tipo 1 humano (HTLV-1) fue el primer retrovirus humano descubierto y se describió por primera vez hace 41 años. Este retrovirus está asociado con el desarrollo de dos enfermedades graves: leucemia/linfoma de células T del adulto (ATLL) e mielopatía asociada a HTLV-1/paraparesia espástica tropical (HAM/TSP). Este estudio tuvo como objetivo analizar las actualizaciones sobre HTLV-1, destacando los aspectos clínicos, los avances y limitaciones en el tratamiento y prevención de la infección por HTLV-1. Para ello, se realizó una revisión integradora, a través de la recolección de datos en las plataformas PubMed, LILACS y SciELO entre marzo y abril de 2021. Se incluyeron 61 artículos de diferentes países. Brasil fue el país con mayor número de publicaciones en el área: 12. Los resultados obtenidos muestran que existen avances efectivos en cuanto al tratamiento y prevención de la infección por HTLV-1. Sin embargo, la falta de estudios específicos sobre el virus que aborden los aspectos clínicos de la infección fue un factor limitante para el presente estudio, lo que refuerza la necesidad de invertir en nuevas investigaciones sobre este virus.

Mielopatía asociada con infección por HTLV-1: paraparesia espástica tropical / Myelopathy associated with HTLV-1 infection: tropical spastic paraparesia

RESUMEN La mielopatía asociada con infección por HTLV-1 o paraparesia espástica tropical (MAH/PET) es una enfermedad crónica degenerativa del sistema nervioso central que afecta principalmente a la médula espinal. Está asociada a la infección por el virus linfotrópico humano tipo 1 (HTLV-1) que pertenece a la familia Retroviridae. América Latina, Asia y África Subsahariana son zonas endémicas de infección por HTLV-1 y MAH/ PET, entre el 2 % y el 17 %, la mayoría asintomáticos. Colombia tiene una alta prevalencia y en especial en su costa pacífica. En las mujeres la infección por HTLV-1 es más prevalente que en los hombres sin que sea clara la causa; se transmite por transfusiones sanguíneas (principalmente de sangre completa), lactancia materna o relaciones sexuales, que es la forma de transmisón más común en pacientes con MAH/PET. La MAH/PET se presenta principalmente en adultos, su periodo de incubación hasta el desarrollo de síntomas varía de dos años hasta décadas. Las principales manifestaciones clínicas de esta enfermedad son la paraparesia y espastici-dad lentamente progresiva que afecta la marcha, asociada con síntomas de esfínteres, como vejiga neurogénica o estreñimiento. Para su diagnóstico se requiere resonancia magnética (RM) de cerebro y médula espinal y la prueba de Elisa, las más usada, con confirmación mediante western blot (WB). En la actualidad no existe un tratamiento específico para la MAH/PET. En el futuro, el uso de biomarcadores ayudará a la detección temprana de la enfermedad e incluso como posible diana terapéutica.

SUMMARY Myelopathy associated with HTLV-1 infection or tropical spastic paraparesis (MAH / PET) is a chronic degenerative disease of the Central Nervous System that mainly affects the spinal cord. It is associated with infection by human lymphotropic virus type 1 (HTLV-1) that belongs to the Retroviridae family. Latin America, Asia and Sub-Saharan Africa are endemic areas of infection by HTLV-1 and MAH / PET between 2 % and 17 %, most asymptomatic. Colombia has a high prevalence and especially on its Pacific coast. In women, HTLV-1 infection is more prevalent than in men without the cause being clear, it is transmitted by blood transfusions (mainly whole blood), breastfeeding and / or sexual intercourse, which is the most common form of transmission in patients with MAH / PET. MAH / PET occurs mainly in adults, its incubation period until the development of symptoms varies from 2 years to decades. The main clinical manifestations of this disease are slowly progressive paraparesis and spasticity affecting gait, associated with sphincter symptoms, such as neurogenic bladder or constipation. For its diagnosis, magnetic resonance imaging (MRI) of the brain, spinal cord and the most used ELISA test are required with confirmation by western blot (WB). Currently there is no specific treatment for HAM / PET. In the future, the use of biomarkers will help early detection of the disease and even as a possible therapeutic target.

Percepção subjetiva de esforço e recuperação da fadiga pós-sessão fisioterapêutica em pacientes com paraparesia espástica tropical / Subjective effort perception and fatigue recovery after physical therapy session in patients with tropical spastic paraparesis

Introdução: Vírus Linfotrópico de Células T Humana do Tipo-1 (HTLV-1) é um retrovírus que afeta os linfócitos T humano e desencadeia inflamação na medula, levando à paraparesia espástica tropical/mielopatia associada ao HTLV-1 (PET/MAH) com prejuízos funcionais. Tais disfunções podem influenciar nos efeitos da fisioterapia, gerando diferentes níveis de fadiga. Objetivo: Avaliar a percepção subjetiva de esforço e de recuperação de indivíduos com PET/MAH após sessão única de fisioterapia. Métodos: Incluíram-se 12 participantes sintomáticos para PET/MAH, de ambos os sexos, que foram submetidos uma vez ao protocolo fisioterapêutico. Os instrumentos avaliativos foram: Escala Modificada de Borg, Escala de Percepção Subjetiva de Recuperação (1º, 5º e 10º minuto após a sessão) e Escala de Incapacidade Neurológica do Instituto de Pesquisa Clínica Evandro Chagas ­ 2 (EIPEC). Resultados: Encontrou-se correlação moderada entre idade e taxa de percepção subjetiva de recuperação ao 1º (r = - 0,4923) e 5º (r = - 0,4913) minuto e entre índice do EIPEC-2 e taxa de percepção subjetiva de recuperação ao 1º (r = 0,3592) e 5º (r = - 0,3772) minuto. Conclusão: Indivíduos deste estudo com maior idade e grau de incapacidade neurológica têm menor percepção subjetiva de recuperação. (AU)

Introduction: Human T-Cell Lymphotropic Virus Type-1 (HTLV-1) is a retrovirus that affects human T lymphocytes and triggers inflammation in the spinal cord, leading to tropical spastic paraparesis / HTLV-1 associated myelopathy (TSP/HAM) with functional impairments. Such dysfunctions can influence the effects of physical therapy, generating different levels of fatigue. Objective: To evaluate the subjective perception of effort and recovery of individuals with TSP/HAM after a single session of physical therapy. Methods: 12 symptomatic participants for TSP/HAM, of both sexes, who were submitted once to a physiotherapeutic protocol were included. The evaluative instruments were: Modified Borg Scale, Scale of Subjective Perception of Recovery (1st, 5th and 10th minute after the session) and Scale of Neurological Disability at the Evandro Chagas Clinical Research Institute - 2 (EIPEC). Results: A moderate correlation was found between age and subjective perception rate of recovery at the 1st (r = - 0.4923) and 5th (r = - 0.4913) minute and between the EIPEC-2 index and the subjective perception rate of recovery at the 1st (r = 0.3592) and 5th (r = - 0.3772) minute. Conclusion: Individuals in this study with older age and degree of neurological disability have less subjective perception of recovery. (AU)

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

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

Human T-cell Lymphotropic Virus and Adult T-cell Leukaemia/Lymphoma: Case Report and Literature Review

ABSTRACT HTLV-I is the first retrovirus directly associated with human malignancy. HTLV-I is endemic in the Caribbean, Japan, parts of Africa, the Middle East and South America. This enveloped double-stranded RNA virus is transmitted by routes similar to HIV, including untested blood/blood product transfusions, sexual contact, intravenous drug abuse, and from mother to child in a vertical transmission. HTLV infection rarely occurs outside of the above sites and very few studies are available globally. Although the retrovirus identified as being associated with chicken sarcoma was described by Rous (1908), the first human retrovirus was not isolated until 1978 from cutaneous T-cell lymphoma in black Americans. Endemicity of the disease in the Caribbean was discovered in 1982 after adult T-cell leukemia (ATL) was found in some London patients, all of Caribbean origin. To date, there is still a lack of studies on the role of viruses in diseases such as inflammatory disorders, arthritis, Sjogren's syndrome, and infectious dermatitis. In Saint Vincent, there were no documented studies that reflected the prevalence and expression of the virus although we did report some cases of HIV-positive HTLV-I ATL. This article discusses the diagnosis and management of a 55-year-old female with an atypical presentation of adult T-cell lymphoma, and we conducted a literature review to determine the prevalence and common presentations of ATL.

Therapeutic effects of virtual reality video gaming on functional mobility, balance, and gait speed in individuals with tropical spastic paraparesis: A randomized crossover clinical trial

Abstract INTRODUCTION: Individuals with human T-cell lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) experience sensorimotor alterations, which can affect functional performance. Virtual reality (VR) videogaming is a therapeutic option, though there is scarce evidence for its use in this population. We aimed to investigate the therapeutic effects of a VR video game on functional mobility, balance, and gait speed in individuals with HAM/TSP. METHODS: We conducted a blinded, crossover clinical trial comprising 29 individuals with HAM/TSP and randomized them into two groups: (1) early therapy: rehabilitative protocol started immediately after the initial evaluation and (2) late therapy: rehabilitative protocol started 10 weeks later. We assessed all participants for balance using the Berg Balance Scale (BBS) scores, functional mobility using the Timed Up and Go (TUG) test, and gait speed using video camera and CvMob software. Differences were considered significant if p<0.05. RESULTS: The early therapy group individuals presented with higher BBS scores (p=0.415), less TUG times (p=0.290), and greater gait speed (p=0.296) than the late therapy group individuals. CONCLUSIONS: VR videogaming is a useful option for rehabilitative therapy in individuals with HAM/TSP; it positively affects balance, functional mobility, and gait speed.

Infección por virus HTLV-1/2 confirmada por serología y detección de provirus en pacientes ecuatorianos de paraparesis espástica tropical / HTLV-1/2 virus infection confirmed by serology and provirus DNA detection in tropical spastic paraparesis Ecuadorian patients

Introduccion: La infección con el virus linfotrópico de células T humano (HTLV) de tipo 1 y 2 es endémica en América del Sur. Existen muy pocos reportes clínicos de este retrovirus en pacientes de Ecuador y nunca confirmaron la presencia del virus con el aislamiento o la detección de su ADN. Esta infección se encuentra desatendida por las autoridades de salud pública, sin que existan estudios epidemiológicos de prevalencia a nivel del país. Objetivos: Este estudio tiene como objetivo la detección de infección por HTLV -1/2 en individuos sintomáticos de paraparesis espástica tropical (TSP) utilizando por primera vez en Ecuador diagnóstico serológico y la detección del provirus por biología molecular. Diseño del estudio. Se tomaron muestras de nueve pacientes con un diagnóstico de mielopatía y sospechoso de TSP, que fueron analizadas para la detección del virus HTLV-1/2 usando tres metodologías: ELISA comercial, ensayo de inmunofluorescencia indirecta (IF) y PCR anidada. Resultados: Cinco de los 9 (55.5%) pacientes fueron positivos tanto para la prueba de ELISA como para IF y PCR anidada. Conclusión: La alta prevalencia de infección por HTLV-1/2 entre individuos sintomáticos de mielopatía muestra la endemicidad de este retrovirus en Ecuador, la asociación de HTLV-1/2 con TSP y la necesidad de implementar estrategias de control y prevención para evitar la diseminación de esta enfermedad infecciosa desatendida.

Background: Infection with the Human T-cell lymphotropic virus (HTLV) type 1 and 2 is endemic in South America. There are only a few clinical reports of this retrovirus in patients in Ecuador, without employing virus-isolation methods or viral DNA detection. The infection is usually neglected in health care settings and by public health authorities and no country wide prevalence data are available. Objectives: This study aims to detect the HTLV-1/2 infection in symptomatic individuals for tropical spastic paraparesis (TSP) using for the first time in Ecuador both immunological and molecular biology methodologies. Study Design: Blood samples of 9 symptomatic individuals with myelopathy were analyzed for the detection of the HTLV-1/2 virus with three methods: ELISA, an indirect immunofluorescence (IF) assay and a nested-PCR. Results: Five out of 9 (55.5%) myelopathy patients were positive for ELISA, IF and nested- HTLV-1/2 PCR. Conclusion. The high prevalence of HTLV-1/2 infection among myelopathy patients shows the endemicity of this retrovirus in Ecuador, the association of HTLV-1/2 infection with TSP and the need of the implementation of control and prevention interventions to overcome the further dissemination of this neglected infectious disease.

The effect of home exercise on the posture and mobility of people with HAM/TSP: a randomized clinical trial / Efeitos de exercícios domiciliares sobre a postura e mobilidade de pessoas com HAM/TSP: ensaio clínico randomizado

Abstract Background: Physical therapy has positive results in people with tropical spastic paraparesis (TSP). However, mobility and distance from rehabilitation centers limit the participation in outpatient programs. Objective: To evaluate the impact of a home exercise program on the posture and functional mobility of people with TSP. Methods: A randomized controlled trial comparing three groups of people who performed guided exercises from a guidebook for six months: supervised (SG), unsupervised (WG), and control (CG). Primary outcomes: postural angles (SAPO®) and functional mobility (TUG). Secondary outcomes: gait parameters (CVMob®). Results: The protocol described in the guidebook improved postural angles and functional mobility. There were also positive gait parameter effects (p<0.05). SG presented better responses than WG did, but both were preferable to CG. Conclusion: Home exercises oriented by a guidebook may benefit posture, functional mobility and gait parameters in people with TSP, and physiotherapist supervision can ensure better results.

Resumo Introdução: A fisioterapia apresenta resultados positivos em pessoas com paraparesia espástica tropical (PET). Entretanto, a dificuldade de locomoção e a distância dos centros de reabilitação limitam a participação em programas ambulatoriais. Objetivo: Avaliar o impacto de um programa de exercícios domiciliares na postura e mobilidade funcional de pessoas com PET. Métodos: Um ensaio clínico randomizado comparou três grupos de pessoas que realizaram exercícios guiados por cartilha: com supervisão (GS), sem supervisão (GN) e controle (GC) durante seis meses. Desfechos primários: ângulos posturais (SAPO®) e mobilidade funcional (TUG). Desfechos secundários: parâmetros da marcha (CVMob®). Resultados: O protocolo descrito na cartilha melhorou os ângulos posturais e a mobilidade funcional. Os resultados também foram positivos para os parâmetros da marcha (p<0,05). O GS apresentou melhores respostas que o GN, porém ambos foram preferíveis ao GC. Conclusão: Exercícios domiciliares orientados por cartilha podem ser úteis para beneficiar a postura, mobilidade funcional e parâmetros de marcha em pessoas com PET, e a supervisão do fisioterapeuta possibilita garantir melhores resultados.

Benefits of inspiratory muscle training under indirect home supervision in patients with human T-cell lymphotropic virus type 1 / Benefícios do treinamento muscular inspiratório sob supervisão indireta domiciliar em pacientes com vírus linfotrópico de células T humana tipo 1

Abstract Introduction: The presence of human T-cell lymphotropic virus type 1 (HTLV-1) associated with neuropathy (myelopathy/tropical spastic paraparesis - HAM/TSP), can generate morphological and functional changes in the respiratory system. As a preventive therapeutic possibility for respiratory dysfunctions, it is expected that the already conceptualized inspiratory muscle training, when performed at home, can be a therapeutic resource that favors adherence to treatment. Objective: To evaluate respiratory muscle strength in patients with HTLV-1 after participating in a home respiratory muscle training protocol under indirect supervision. Method: This was a clinical, longitudinal, prospective, quantitative, and single-center trial approved by the Research Ethics Committee of the State University of Pará, opinion no. 2.695.505 and registered in clinical trials NCT03829709. Six HTLV-1 patients participated in a 5-week home respiratory muscle training protocol lasting 30 minutes daily through a linear load inspiratory muscle trainer. For the characterization of the imposed load, they were submitted to manovacuometry during pre (T0), peri (T3), and post (T5) treatment. Results: Six individuals completed the program, of which 83.33% were female and 16.66% male. With the application of respiratory muscle training, it was possible to achieve a significant increase (p < 0.011) of the maximum inspiratory pressure as shown when comparing T0 (66.8±12.58) to T5 (115.08±31.78). Conclusion: This study identified an increase in inspiratory muscle strength after HTLV-1 patients participated in a home muscle training protocol under indirect supervision.

Resumo Introdução: A presença do vírus linfotrópico de células T humana do tipo 1 (HTLV-1) associado à neuropatia (Paraparesia Espástica Tropical/Mielopatia - PET/MAH) pode gerar alterações morfológicas e funcionais no sistema respiratório. Como possibilidade terapêutica preventiva para disfunções respiratórias, vislumbra-se que o treinamento muscular inspiratório já conceituado, possa a nível domiciliar ser uma ferramenta terapêutica que favoreça a adesão ao tratamento. Objetivo: Avaliar a força muscular respiratória diante de um protocolo de treinamento muscular respiratório domiciliar, sob supervisão indireta em portadores do HTLV- 1. Método: Estudo clínico, longitudinal, prospectivo, quantitativo e de centro único, aprovado pelo Comitê de Ética em Pesquisa da Universidade do Estado do Pará, parecer no. 2.695.505 e registrado no Clinical Trials NCT03829709. Seis pacientes com HTLV-1 participaram de um protocolo de treinamento muscular respiratório domiciliar por 5 semanas com duração de 30 minutos diários por meio de um treinador muscular inspiratório de carga linear. Para a caracterização da carga imposta, os mesmos foram submetidos a manovacuometria, pré (T0), peri (T3) e pós (T5) tratamento. Resultados: Seis indivíduos completaram o programa, dos quais 83.33% eram do sexo feminino e 16.66% do sexo masculino. Com a aplicação do treinamento muscular respiratório foi possível obter um aumento significativo (p < 0,011) da pressão inspiratória máxima ao comparar T0 (66.8±12.58) ao T5 (115.08±31.78). Conclusão: Este estudo identificou um aumento na força muscular inspiratória após pacientes com HTLV-1 participarem de um protocolo de treinamento muscular domiciliar sob supervisão indireta.

Center of gravity oscillations in HTLV-1-associated myelopathy/tropical spastic paraparesis / Oscilações do centro de gravidade na mielopatia associada ao HTLV-1/ paraparesia espástica tropical / Oscilaciones del centro de gravedad en la mielopatía asociada al HTLV-1/paraparesia espástica tropical

Abstract Introduction: Postural control in individuals with HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is usually compromised, which increases the risk of falls, makes it difficult to perform activities of daily living, and impairs the quality of life. The profile of the center of gravity oscillations in this population is unknown and may aid in clinical follow-up and research. Objective: To compare the stabilometric values between HAM/TSP and uninfected individuals and verify the existence of correlations between stabilometric variables and the Berg Balance Scale (BBS). Method: A cross-sectional observational study was performed with infected individuals, classified as defined and likely (WHO criteria), compared to accompanying persons and seronegative relatives. A baropodometry platform (Footwork®) was used to obtain the oscillation values of the body's center of gravity in total oscillation area (TOA), anterior-posterior oscillation (APO) and lateral oscillation (LO). Mean values were correlated with BBS by Spearman's Correlation (5% alpha). Approved by the ethical committee of Escola Bahiana de Medicina e Saúde Pública under Opinion 49634815.2.0000.5628. Results: An asymmetric distribution of all the stabilometric variables analyzed in the HAM/TSP population was found, different from the uninfected group (p < 0.05). It was also possible to verify strong to moderate and inverse correlations between the variables of center of gravity oscillation with the scores obtained in BBS, especially for TOA and LO. Conclusion: People with HAM/TSP presented higher values for the center of gravity oscillations and these were correlated with the BBS in the balance evaluation.

Resumo Introdução: o controle postural em indivíduos com mielopatia associada ao HTLV-1 ou paraparesia espástica tropical (HAM/TSP) é geralmente comprometido, o que aumenta o risco de quedas, dificulta a realização de atividades de vida diária e prejudica a qualidade de vida. O perfil das oscilações do centro de gravidade nesta população é desconhecido e pode auxiliar no acompanhamento clínico e na pesquisa. Objetivo: comparar os valores estabilométricos entre pessoas com HAM/TSP e não infectados, e verificar a existência de correlações entre variáveis estabilométricas e a Escala de Equilíbrio Berg (EEB). Método: foi realizado um estudo observacional transversal com indivíduos infectados, classificados como definidos e prováveis (critérios da OMS), comparados com acompanhantes e familiares soronegativos. Uma plataforma de baropodometria (Footwork®) foi utilizada para obter os valores de oscilação do centro de gravidade do corpo em área de oscilação total (AOT), oscilação anteroposterior (OAP) e oscilação laterolateral (OLL). Os valores médios foram correlacionados com a BBS pela Correlação de Spearman (alfa 5%). Aprovado pelo Comitê de Ética da Escola Bahiana de Medicina e Saúde Pública sob o CAAE 49634815.2.0000.5628. Resultados: encontrou-se distribuição assimétrica de todas as variáveis estabilométricas analisadas na população com HAM/TSP, diferentes do grupo de não infectados (p < 0,05). Também foi possível verificar correlações de forte a moderada e inversas entre as variáveis de oscilação do centro de gravidade com os escores obtidos na EEB, especialmente para AOT e OLL. Conclusão: Pessoas com HAM/TSP apresentaram valores maiores para as oscilações do centro de gravidade e estas foram correlacionadas com a EEB na avaliação do equilíbrio.

Resumen Introducción: El control postural en individuos con mielopatía asociada al HTLV-1 o paraparesia espástica tropical (HAM/TSP) suele estar comprometido, lo que aumenta el riesgo de caídas, les dificulta en las actividades de la vida diaria y perjudica su calidad de vida. Conocer el perfil de las oscilaciones del centro de gravedad en esta población puede ayudar en el seguimiento clínico y la investigación. Objetivo: Comparar los valores estabilométricos entre personas con HAM/TSP y personas no infectadas, y verificar la existencia de correlaciones entre las variables estabilométricas y la Escala de Equilibrio de Berg (BBS). Método: Se realizó un estudio observacional transversal con individuos infectados, clasificados como definidos y probables (criterios de la OMS), comparados a acompañantes y familiares seronegativos. Se utilizó una plataforma de baropodometría (Footwork®) para obtener los valores de oscilación del centro de gravedad del cuerpo en el área de oscilación total (AOT), oscilación antero-posterior (OAP) y oscilación lateral-lateral (OLL). Los valores medios se correlacionaron con la BBS por la correlación de Spearman (alfa 5%). Estudio aprobado por el Comité de Ética de la Escuela Bahiana de Medicina y Salud Pública bajo CAAE 49634815.2.0000.5628. Resultados: Se encontró una distribución asimétrica de todas las variables estabilométricas analizadas en la población HAM/TSP diferente en el grupo no infectado (p <0,05). También fue posible verificar correlaciones de fuertes a moderadas e inversas entre las variables de oscilación del centro de gravedad con las puntuaciones obtenidas en la BBS, especialmente para AOT y OLL. Conclusión: Las personas con HAM/TSP presentaron valores más altos en las oscilaciones del centro de gravedad, las cuales se correlacionaron con la BBS en la evaluación del equilibrio.

Balance assessment in HTLV-1 associated myelopathy or tropical spastic paraparesis

Abstract INTRODUCTION: A good rating of the device in people with HTLV-1 in this population is essential for accuracy in prescribing data (walking). Thus, this study aimed to analyze the counterpart assessment methods that are best suited to patients with human T-cell lymphotropic virus (HTLV)-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). METHODS: This cross-sectional study related stabilometric and kinematic variables of postural oscillations with Berg's balance scale (BBS) and Timed Up and Go (TUG) in subjects with HAM/TSP compared to asymptomatic subjects. To assess the posterior and lateral postural projection, baropodometry and the Footwork® system was used, and the CVMob system was applied to kinematic parameters. The means comparison tests and correlations were applied with an alpha of 5%. RESULTS: Thirty-nine subjects (predominantly female) made up the sample. There was an increase in barodopometric oscillations, in the total oscillation area (p = 0.004), in the anteroposterior oscillation in the left (p = 0.015) and right views (p = 0.036), and in the lateral oscillation (p = 0.039) in the HAM/TSP group. Moderate correlations were found between oscillation baropodometry and the angular variation of the ankle, as well as with the BBS in the three angles and the TUG for lateral oscillation (p = 0.406). CONCLUSIONS: Each method has advantages and disadvantages, including cost accuracy. The best resources available at no additional cost for outpatient to use are the kinematic evaluation using a simple smartphone camera and free analysis software, and the TUG.

Infección Por El Virus Linfotrópico De Células T Humano HTLV-1 Y Paraparesis Espástica Tropical En Ecuador: Paradigma De Enfermedad Tropical Desatendida / Human T-lymphotrophic Virus Infection (HTLV-1) And Tropical spastic Paraparesis: Paradigms Of An Overlooked Tropical Disease

Resumen La infección por el virus linfotrópico de células T humano de tipo 1 (HTLV-1) es considerada endémica en América del Sur. Desde hace más de dos décadas existen reportes de casos clínicos de mielopatías asociadas a infección por el retrovirus HTLV-1 en pacientes de Ecuador, patología denominada paraparesis espástica tropical. Sólo hay dos estudios de seroprevalencia de HTLV-1 en Ecuador, ambos con tamaños muestrales pequeños pero en ambos casos indicativos de una alta prevalencia de HTLV-1, al menos comunidades afrodescendientes e indígenas de Ecuador. Pese a ello, y a diferencia de países vecinos, no se realiza tamizaje de bancos de sangre y órganos por parte de las autoridades sanitarias competentes. Por tanto, esta infección y las patologías asociadas a la misma (como la paraparesis espástica tropical) se encontrarían desatendidas y sub diagnosticadas. En definitiva, urge desarrollar estudios epidemiológicos de prevalencia a nivel del país e implementar estrategias de control y prevención para evitar la diseminación de esta infección.

Abstract The human T cell lymphotropic virus (HTLV-1) infection is considered endemic in South America. For more than two decades clinical cases of HTLV-1 associated mielopaties have been reported in Ecuador, pathology known as tropical spastic paraparesis. There is only two studies about HTLV-1 seroprevalence in Ecuador, both of them with small sample size but showing a high prevalence of HTLV-1 infection, at least for afrodescendants and indigenous communities. Howewer, there is not a currently screening for blood and organ banks carried out by ecuadorian public health authorities. This scenario makes HTLV-1 infection and associated pathologies (like tropical spastic paraparesis) neglected diseases in Ecuador. More epidemiological studies need to be implemented in order to develope control and prevention strategies in the country.

Neurologic complications of HTLV-1: a review / Complicações neurológicas do HTLV: uma revisão HTLV-1

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.

Parâmetros para reabilitação da marcha em pessoas com Paraparesia Espástica Tropical: estudo transversal / Parameters for gait rehabilitation in Tropical Spastic Paraparesis: cross sectional study

INTRODUÇÃO: A marcha de pessoas com Mielopatia Associada ao HTLV-1 ou Paraparesia Espástica Tropical (HAM/TSP) é pouco conhecida. OBJETIVO: Avaliar o perfil cinemático da marcha em pessoas com HAM/TSP. MÉTODOS: Estudo transversal com 25 pessoas com HAM/TSP e 25 participantes saudáveis. Os dados espaço-temporais e angulares das filmagens da marcha foram submetidos à análise cinemática utilizando o software CVMob®. A marcha dos participantes com HAM/TSP foi analisada quantitativamente através do teste t-student (alfa de 5% e poder de 80%). O projeto foi aprovado pelo comitê de ética da Escola Bahiana de Medicina e Saúde Pública sob o CAAE 13568213.8.0000.5544. RESULTADOS: O grupo HAM/TSP apresentou alterações significativas em dois domínios distintos da análise biomecânica da marcha quando comparados aos controles saudáveis. As variáveis angulares apresentaram maior inclinação, flexão e extensão do tronco (p <0,05); aumento da flexão do quadril e diminuição da extensão do quadril (p <0,05); diminuição da flexão e extensão do joelho (p <0,05); diminuição da flexão dorsal e plantar do tornozelo (p <0,05). A amplitude de movimento também foi reduzida em todas essas articulações. As variáveis espaço-temporais mostraram diminuição do comprimento da passada, aumento do tempo da passada e velocidade do ciclo da marcha (p <0,001). Essas mudanças apontam para redução nas amplitudes articulares do quadril, joelho e tornozelo, mudanças na base de apoio e assimetria do tempo do duplo apoio entre os lados direito e esquerdo, redução do tempo do pré-balanço, elevação do quadril no balanço médio e queda do pé ao longo do balanço. CONCLUSÃO: As pessoas com HAM/TSP apresentam marcha caracterizada por redução nas amplitudes articulares do quadril, joelho e tornozelo, assimetria do tempo de suporte duplo entre os lados direito e esquerdo, redução do tempo do pré-balanço, elevação do quadril no balanço médio e queda do pé ao longo do balanço.

INTRODUCTION: The gait in people with HTLV-1 Associated Myelopathy or Tropical Spastic Paraparesis (HAM / TSP) is little known. OBJECTIVE: To evaluate the kinematic profile of gait in people with HAM/ TSP. METHODS: A cross-sectional study with 25 people with HAM/TSP and 25 healthy participants. Spatiotemporal and angular data from filming of gait were submitted to kinematic analysis using CVMob® software. The gait of partipants with HAM/TSP was analized quantitatively through t Student test (alpha 5% and Power of 80%). The project was approved by Ethical Committee of the Bahiana School of Medicine and Public Health with CAAE 13568213.8.0000.5544. RESULTS: The HAM/TSP group showed significant changes in two different domains of biomechanical gait analysis when compared to healthy controls. The angular variables showed increased trunk inclination, flexion and extension (p<0.05); increased hip flexion and decreased hip extension (p<0.05); decreased knee flexion and extension (p<0.05); decreased ankle dorsi and plantar flexion (p<0.05). Range of Motion was also reduced in all those joints. The spatiotemporal variables showed decreased stride length, increased stride time and speed gait cycle (p<0.001). Those changes point out to reduction in joint amplitudes of hip, knee and ankle, changes in support base and double support time asymmetry between right and left sides, reduction of pre-swing time, hip lift in the mid-swing, and foot drop throughout the swing. CONCLUSION: People with HAM/TSP have gait characterized by reduction in joint amplitudes of hip, knee and ankle, asymmetry between right and left sides and reduction of pre-swing time, hip lift in the mid-swing, and foot drop throughout the swing.

Low frequency of regulatory B-cells and increased CD4+ and CD8+ interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type

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.

Alterações sensoriais em indivíduos com HTLV-1: revisão sistemática / Sensorial changes in individuals with HTLV-1: systematic review

Introdução: A função sensorial é reconhecida como precursora da recuperação do movimento, sendo assim, os sintomas apresentados por pessoas com HTLV-1 podem trazer prejuízo na realização de atividades funcionais Objetivo: Sistematizar o conhecimento sobre alterações sensoriais em pacientes com HTLV-1. Metodologia: Trata-se de uma revisão sistemática, com a busca primária dos artigos realizada nas bases de dados Medline, via biblioteca virtual Pubmed, sendo incluídos estudos observacionais que abordaram a alteração sensorial em indivíduos com HTLV-1. A estratégia de busca foi conduzida de forma independente por dois pesquisadores e as divergências resolvidas por consenso. Resultados: Foram encontrados 44 estudos na busca primária, e destes foram incluídos quatro estudos que abordaram a alteração sensorial em indivíduos com HTLV-1, com um total de 240 participantes. Todos os artigos foram classificados como baixo risco de viés no que diz respeito à descrição da questão do estudo, resultados e discussão. Conclusão: identificou-se uma alta prevalência de dor e alteração na sensibilidade vibratória em relação às outras disfunções sensoriais, no entanto, a escassez de trabalhos publicados acerca deste tema sugere que novas abordagens sejam feitas mostrando uma grande lacuna de conhecimento a ser explorada. [AU]

Background: Sensory function is recognized as a precursor of the movement recovery. Therefore, the symptoms presented by people with HTLV-1 can result in impairment in the performance of functional activities. Aim: To systematize knowledge about sensory alterations in patients with HTLV-1. Methods: This is a systematic review, with the primary search of the articles carried out in the Medline databases, via the Pubmed virtual library, including observational studies that addressed the sensory alteration in individuals with HTLV-1. The search strategy was conducted independently by two researchers and the divergences resolved by consensus. Results: A total of 44 studies were found in the primary search, including four studies addressing sensory impairment in individuals with HTLV-1, with a total of 240 participants. All articles were classified as low risk of bias regarding the description of the study question, results and discussion. Conclusion: We identified a high prevalence of pain and altered vibratory sensitivity in relation to other sensory disorders, however, shortage of published works on this topic suggests new approaches are made showing a large knowledge gap to be explored. [AU]