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La tuberculosis es una infección de alta incidencia en Latinoamérica. Su presentación como infección activa está determinada por factores de riesgo del hospedero. Comunicamos el caso clínico de una mujer joven que presentó una forma grave de tuberculosis pulmonar. Al explorar sus factores de riesgo se confirmó un estado de inmunosupresión profundo, causado por un linfoma de células T, asociada a una co-infección por virus linfotrópico T humano tipo 1. Se destacan los aspectos microbiológicos y de pronóstico de la co-infección de Mycobacterium tuberculosis y HTLV-1
Tuberculosis is a high-incidence infection in Latin America. Its presentation as an active infection is determined by risk factors in the host. We report the case of a young woman who presented a severe form of pulmonary tuberculosis. When exploring her risk factors, a profound state of immunosuppression was found, caused by T-cell lymphoma, associated with co-infection with human lymphotropic virus. Microbiological and prognostic aspects of Mycobacterium tuberculosis and HTLV-1 co-infection are highlighted.
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Humanos , Femenino , Persona de Mediana Edad , Tuberculosis Pulmonar/complicaciones , Infecciones por HTLV-I/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen , Virus Linfotrópico T Tipo 1 Humano , Infecciones por HTLV-I/diagnóstico por imagen , Leucemia de Células T/complicaciones , Huésped Inmunocomprometido , Resultado Fatal , Coinfección , Mycobacterium tuberculosisRESUMEN
ABSTRACT The human T-cell lymphotropic virus type 1 (HTLV-1) is a single-stranded positive-sense RNA virus that belongs to the Retroviridae family, genus Deltaretro, and infects approximately five to 10 million people worldwide. Although a significant number of individuals living with HTLV-1 remain asymptomatic throughout their lives, some develop one or more severe clinical conditions, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive and debilitating disease, and/or a subtype of non-Hodgkin's lymphoma with a more threatening course known as adult T-cell leukemia/lymphoma (ATLL). Moreover, current therapeutic options are limited and focus primarily on treating symptoms and controlling viral latency. CRISPR-Cas9 gene editing is proposed as a promising tool to address the intricate links associated with HTLV-1. By targeting or silencing key genes during initial infection and dysregulating immune signaling pathways, CRISPR-Cas9 offers potential intervention opportunities. In this review, we address the therapeutic potential of CRISPR-Cas9 gene editing, as well as examine the primary mechanisms involved in editing potential target genes and discuss the existing evidence in the current scientific literature.
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Introducción: El Perú es endémico al virus linfotrópico T humano tipo 1 (HTLV-1), por esas razones es importante conocer la fiabilidad de las pruebas diagnósticas que se usan en el país, con la finalidad de continuar o no su uso. El objetivo fue evaluar el rendimiento de tres pruebas serológicas ELISA Murex, ELISA Wantai e IFI INS-Perú para la detección de anticuerpos anti HTLV-1 frente a muestras peruanas. El estudio. Las tres pruebas fueron evaluadas frente a 382 sueros: 215 positivos y 167 negativos a HTLV-1 (Gold Standar: inmunoblot). Hallazgos. IFI no presentó falsos positivos, Wantai tuvo más falsos negativos (siete) y Murex más falsos positivos (ocho). Las tres pruebas mostraron resultados superiores a 95% para los parámetros estimados de exactitud diagnóstica. Conclusiones. IFI INS-Perú y ELISA Murex tuvieron buen rendimiento diagnóstico para la detección de anticuerpos contra HTLV-1 y son buenos candidatos para continuar siendo usados en Perú.
Background: Peru is endemic to the human T-lymphotropic virus type 1 (HTLV-1), for these reasons it is important to know the reliability of the diagnostic tests used in the country, in order to continue their use or not. The objective was to evaluate the performance of three serological tests ELISA Murex, ELISA Wantai and IFI INS-Peru for the detection of anti-HTLV-1 antibodies against Peruvian samples. The study. The three tests were evaluated against 382 sera: 215 positive and 167 negative for HTLV-1 (Gold Standard: immunoblot). Findings. IFI had no false positives, Wantai had more false negatives (seven) and Murex more false positives (eight). The three tests showed results above 95% for the estimated parameters of diagnostic accuracy. Conclusions. IIF INS-Perú and ELISA Murex had good diagnostic performance for the detection of antibodies against HTLV-1 and are good candidates to continue being used in Peru.
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Introdução: a paraparesia espástica tropical ou mielopatia associada ao HTLV (HAM/TSP) é umadoença infecciosa e inflamatória crônica, que pode interferir em vários aspectos da vida do indivíduo e, com isso, alterar sua qualidade de vida (QV). Objetivo: avaliar os domínios da escala SF-36 que mais contribuem para as alterações na qualidade de vida dos pacientes com HAM/TSP. Metodologia: nesse estudo observacional, transversal e quantitativo, realizado com 49 pacientes diagnosticados com HAM/TSP do setor de Neurociências do Ambulatório Professor Francisco Magalhães Neto, na cidade de Salvador, Bahia, Brasil, a qualidade de vida foi avaliada pelo questionário de saúde Short Form-36 (SF-36), no período de fevereiro de 2019 a julho de 2020, e de fevereiro de 2022 a abril de 2022. Os dados obtidos foram avaliados por análise estatística descritiva e testes de correlação de Pearson e Spearman. Resultados: foi observado que os menores escores do questionário SF-36, indicando pior qualidade de vida, foram relativos aos domínios vinculados às limitações físicas, capacidades funcionais e limitações emocionais, nessa ordem. Os melhores domínios, indicando melhor qualidade de vida, nessa população, foram saúde mental e aspectos sociais, demostrando que os pacientes com HAM/TSP relatam alterações físicas e emocionais em sua qualidade de vida. Conclusão:os domínios que mais alteraram a qualidade de vida dos pacientes com HAM/ TSP foram AF, CF e AE. Assim, utilizando-se da escala SF-36, profissionais de saúde podem identificar e intervir precocemente em domínios que comprometam a saúde física e emocional dos pacientes com HAM/TSP, alterando, consequentemente, sua qualidade de vida.
Introduction: tropical Spastic Paraparesis or HTLV-associated Myelopathy (HAM/TSP) is a chronic infectious and inflammatory disease that can interfere with various aspects of individuals life and, thereby alter their Quality of Life (QoL). Objective: to evaluate the domains of the sf-36 scale that most contribute to changes in the quality of life of patients with HAM/TSP. Methods: in this observational, cross-sectional and quantitative study carried out with 49 patients diagnosed with HAM/TSP from the Neuroscience sector of the Professor Francisco Magalhães Neto Ambulatory, in the city of Salvador, Bahia, Brazil, quality of life was assessed using the Short Form Health Questionnaire Form 36 (SF-36), from February/19 to July/20 and from February/22 to April/22. Data obtained were evaluated by descriptive statistical analysis and Pearson and Spearman correlation tests. Results: it was observed that the lowest scores on the SF-36 questionnaire, indicating worse quality of life, were related to the domains linked to physical limitations, functional capacities and emotional limitations, in that order. The best domains, indicating better quality of life in this population, were mental health and social aspects, showing that patients with HAM/TSP report physical and emotional changes in their quality of life. Conclusion: the domains that most changed the quality of life of patients with HAM/TSP were PA, FC and EA. Thus using the SF-36 scale, health professionals can identify and intervene early in areas that compromise the physical and emotional health of patients with HAM/TSP, consequently altering their quality of life.
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Humanos , Masculino , Femenino , Adulto , Calidad de Vida , Enfermedades de la Médula Espinal , Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Salud Mental , Estudios Transversales , Estudios de Evaluación como AsuntoRESUMEN
El HTLV-1 es un retrovirus que afecta principalmente a los linfocitos T-CD4, causando enfermedades como paraparesia espástica o mielopatía, uveítis, dermatitis infecciosas, leucemia/linfoma de las células T del adulto, además de otras enfermedades. Causa una infección crónica de por vida en humanos y su transmisión ocurre a través de la lactancia materna, el contacto sexual y las transfusiones de sangre. En Chile actualmente ocupa el cuarto lugar en notificaciones entre el año 2014-2021, estimándose a nivel mundial más de 20 millones de portadores. El mayor riesgo de transmisión ocurre por lactancia mayor a seis meses y alta carga proviral y altos títulos de anticuerpos en la madre portadora. El objetivo consistió en analizar la situación de la portación del virus HTLV-1 durante el embarazo, determinando su prevalencia, vías de transmisión y complicaciones. Se realizó una revisión bibliográfica sistemática de artículos publicados en bases de datos científicas referidos al virus HTLV-1. Este virus está globalmente diseminado y se presenta en forma endémica en algunas regiones del mundo con prevalencias entre muy elevadas y bajas. En Chile la seroprevalencia en promedio es de 0,124% para HTLV-1. Esta infección no cuenta con tratamiento, solo se tratan los síntomas por lo que mientras esto no cambie, solo es factible reducir la transmisión, incidencia y la morbilidad del HTLV-1 incorporando medidas de control del virus en las intervenciones de control de enfermedades y estrategias de salud pública. La forma más eficiente de transmisión del virus madre-hijo es a través de la leche materna, es necesario implementar la detección prenatal de HTLV-1, en especial en las zonas endémicas, así como también asesorar a las madres HTVL-1 positivas sobre la lactancia materna.
HTLV-1 is a retrovirus that mainly affects CD4-T lymphocytes, causing diseases such as spastic paraparesis or myelopathy, uveitis, infectious dermatitis, adult T-cell leukemia/lymphoma, and other diseases. It causes a lifelong chronic infection in humans and its transmission occurs through breastfeeding, sexual contact and blood transfusions. In Chile, it currently ranks fourth in notifications between the years 2014-2021, with more than 20 million carriers being estimated worldwide. The greatest risk of transmission occurs by breastfeeding for more than six months and high proviral load and high antibody titers in the carrier mother. The objective consisted of analyzing the situation of the carriage of the HTLV-1 virus during pregnancy, determining its prevalence, transmission routes and complications. A systematic bibliographic review of articles published in scientific databases referring to the HTLV-1 virus was carried out. This virus is globally disseminated and occurs endemic in some regions of the world with prevalence between very high and low. In Chile, the average seroprevalence is 0.124% for HTLV-1. There is no treatment for this infection, only the symptoms are treated, so as long as this does not change, it is only feasible to reduce the transmission, incidence, and morbidity of HTLV-1 by incorporating virus control measures into disease control interventions and strategies. of public health. The most efficient form of mother-child transmission of the virus is through breast milk, it is necessary to implement prenatal screening for HTLV-1, especially in endemic areas, as well as counsel HTLV-1 positive mothers on breastfeeding
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Humanos , Femenino , Embarazo , Virus Linfotrópico T Tipo 1 Humano , Chile/epidemiología , Prevalencia , Transmisión Vertical de Enfermedad InfecciosaRESUMEN
RESUMEN La mielopatía asociada con infección por HTLV-1 o paraparesia espástica tropical es una enfermedad crónica degenerativa del sistema nervioso central que afecta principalmente la médula espinal, una enfermedad rara en nuestro medio. El caso se trata sobre una mujer de 65 años, que acude con un cuadro de 2 años de evolución con disminución de la fuerza muscular de miembros inferiores progresiva hasta impedir la marcha, se acompaña de incontinencia urinaria y fecal, y hormigueo en miembros inferiores. Examen físico neurológico: disminución de fuerza muscular en miembros inferiores (2/5), reflejos osteotendinosos exaltados en miembros inferiores, Babisnky bilateral, hipostesia en cara lateral de piernas y dorso y planta de los pies, clonus patelar, y sin nivel sensitivo. En estudios paraclínicos: líquido cefalorraquídeo con cito químico (proteínas ligeramente aumentada) y citológico normal, ausencia de bandas oligoclonales, serología HIV negativo, perfil autoinmune negativo. Electromiografía normal, tomografía de cráneo, tórax y abdomen normal. Resonancia magnética cerebral y medular normal al principio, los cuales fueron repetidos al cabo de 8 meses y se observan lesiones inflamatorias en cerebro y médula espinal. PCR (reacción en cadena de la polimerasa) en sangre para HLTV-1 positiva. La paciente fue tratada con pulsos de metilprednisolona, seguido de prednisona oral y azatioprina por 3 meses sin respuesta favorable y con efectos secundarios a los corticoides por lo que se suspende. Se inició inmunoglobulina IV 400mg kg/p/mensual por 3 meses, sin respuesta. Se inicia rituximab 500mg cada 15 días hace 1 mes y evaluar la respuesta en los controles sucesivos. Conclusión: La mielopatía asociada a virus linfotrópico humano de células T tipo 1(HTLV-1) o paraparesia espástica tropical (MAH/PET), debe ser considerado en el diagnóstico diferencial en un paciente con mielopatia en el Paraguay.
ABSTRACT Myelopathy associated with HTLV-1 infection or tropical spastic paraparesis is a chronic degenerative disease of the central nervous system that mainly affects the spinal cord, a rare disease in our setting. The case is about a 65-year-old woman, who presented with a 2-year history of progressive decrease in muscle strength of the lower limbs until it prevented her from walking, accompanied by urinary and fecal incontinence, and tingling in the lower limbs. Neurological physical examination: decreased muscle strength in the lower limbs (2/5), increased osteotendinous reflexes in the lower limbs, bilateral Babinky, hypoesthesia in the lateral aspect of the legs and the back and soles of the feet, patellar clonus, and no sensory level. In paraclinical studies: normal cytochemical and cytological cerebrospinal. Fluid (slightly increased protein), absence of oligoclonal bands, negative HIV serology, negative autoimmune profile. Normal electromyography, tomography of the skull, thorax and normal abdomen. Magnetic resonance imaging of the brain and spinal cord was normal at the beginning, which were repeated after 8 months, and inflammatory lesions in the brain and spinal cord were observed. PCR (polymerase chain reaction) in blood for HLTV-1 positive. The patient was treated with methylprednisolone pulses, followed by oral prednisone and azathioprine for 3 months without a favorable response and with corticosteroid side effects, so she was discontinued. IV immunoglobulin 400mg kg/p/monthly for 3 months was started, with no response. Rituximab 500mg every 15 days was started 1 month ago and the response was evaluated in successive controls. Conclusion: myelopathy associated with human T-cell lymphotropic virus type 1 (HTLV-1) or tropical spastic paraparesis (MAH/PET), should be considered in the differential diagnosis in a patient with myelopathy in Paraguay.
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The present study aims to correlate the sample-to-cutoff ratios (S/CO) distributions of reactive results for HTLV-1/2 antibodies with the detection of proviral DNA in a population of blood donor candidates. It was carried out a retrospective data search of 632 HTLV-1/2 reactive samples, submitted to confirmatory testing from January 2015 to December 2019. Serological screening was performed by chemiluminescent microparticle immunoassay Architect rHTLV-I/II, whereas confirmatory testing was performed by in-house real-time polymerase chain reaction method. 496 out of 632 samples (78%) had undetectable HTLV-1/2 proviral DNA and 136 (22%) had detectable proviral DNA. HTLV infection was not confirmed in any individual for whom the S/CO ratio value was <4, and proviral DNA detection rates gradually escalated as S/CO ratio values increased. The sensitivity and predictive positive value found for the Architect rHTLV-I/II was 100% and 22%, respectively. The receiver operating characteristic (ROC) curve analysis showed that the optimal S/CO ratio value for predicting the presence of HTLV-1/2 was 18.11. High S/CO ratios were more associated with the detection of proviral DNA. The S/CO ratio value <4 suggests excluding true HTLV infection and the risk of blood transmission (AU).
O estudo tem como objetivo correlacionar às distribuições das razões sample-to-cutoff (S/CO) de resultados reagentes para anticorpos HTLV-1/2 com a detecção de DNA proviral em uma população de candidatos à doação de sangue. Realizou-se uma busca retrospectiva de dados de 632 amostras reagentes para HTLV-1/2 submetidas à testagem confirmatória entre janeiro de 2015 a dezembro de 2019. A triagem sorológica foi realizada pelo imunoensaio quimioluminescente de micropartículas Architect rHTLV-I/II, enquanto o teste confirmatório foi realizado pelo método de PCR em tempo real in-house. 496 de 632 amostras (78%) apresentaram DNA proviral indetectável e 136 (22%) apresentaram DNA proviral detectável. A infecção por HTLV não foi confirmada em nenhum indivíduo com valor de S/CO <4 e as taxas de detecção de DNA proviral escalonaram gradualmente à medida que as razões S/CO aumentaram. A sensibilidade e valor preditivo positivo encontrados para o Architect rHTLV-I/II foram 100% e 22%, respectivamente. Utilizando análise de curva ROC, o valor de razão S/CO ideal para predizer a presença de DNA proviral foi de 18,11. Razões S/CO elevadas foram mais associadas à detecção de DNA proviral. Em suma, o valor de S/CO <4 sugere a exclusão de infecção por HTLV e o risco de transmissão pelo sangue (AU).
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Donantes de Sangre , Inmunoensayo , Virus Linfotrópico T Tipo 1 Humano , Virus Linfotrópico T Tipo 2 Humano , Reacción en Cadena en Tiempo Real de la Polimerasa , InfeccionesRESUMEN
The patient was a 76-year-old woman who developed involuntary movements in both hands and gait disorder. Weakness in both lower limbs gradually worsened, and she was referred to our hospital. Neurological findings included spastic paraplegia, deep sensory disturbance, sensory ataxia, and bladder and bowel dysfunction. Approximately 4 months after the onset, she became unable to walk independently and had to use a walker. MRI showed a long spinal cord lesion extending from the cervical to thoracic spinal cord. Blood and spinal fluid samples tested positive for anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies. Given these findings and subacute course, she was diagnosed with rapidly progressive HTLV-1 associated myelopathy (HAM). High levels of neopterin and CXCL10 in the cerebrospinal fluid suggested high disease activity;thus, she underwent steroid pulse therapy followed by treatment with maintenance oral prednisolone in our convalescent rehabilitation ward. After approximately 3 months of muscle strength training, mainly for the trunk muscle and the proximal muscle of the lower limbs, and balance exercise, she was able to walk independently and her activities of daily living (ADL) and instrumental ADL (IADL) improved;however, dysuria persisted. The use of clean intermittent self-catheterization instead of indwelling urethral catheter improved her quality of life (QOL). Although rapidly progressive HAM is generally associated with poor prognosis, steroid therapy combined with comprehensive rehabilitation treatment was effective in the present case.
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The patient was a 76-year-old woman who developed involuntary movements in both hands and gait disorder. Weakness in both lower limbs gradually worsened, and she was referred to our hospital. Neurological findings included spastic paraplegia, deep sensory disturbance, sensory ataxia, and bladder and bowel dysfunction. Approximately 4 months after the onset, she became unable to walk independently and had to use a walker. MRI showed a long spinal cord lesion extending from the cervical to thoracic spinal cord. Blood and spinal fluid samples tested positive for anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies. Given these findings and subacute course, she was diagnosed with rapidly progressive HTLV-1 associated myelopathy (HAM). High levels of neopterin and CXCL10 in the cerebrospinal fluid suggested high disease activity;thus, she underwent steroid pulse therapy followed by treatment with maintenance oral prednisolone in our convalescent rehabilitation ward. After approximately 3 months of muscle strength training, mainly for the trunk muscle and the proximal muscle of the lower limbs, and balance exercise, she was able to walk independently and her activities of daily living (ADL) and instrumental ADL (IADL) improved;however, dysuria persisted. The use of clean intermittent self-catheterization instead of indwelling urethral catheter improved her quality of life (QOL). Although rapidly progressive HAM is generally associated with poor prognosis, steroid therapy combined with comprehensive rehabilitation treatment was effective in the present case.
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Abstract Background: Joint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 +and CD8 +positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain. Methods: Cross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles. Results: Eighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls ( p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) ( p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals ( p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group. Conclusion: HTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.
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ABSTRACT Interferon-gamma (IFN-γ) plays a crucial role in viral infections by preventing viral replication and in the promotion of innate and adaptive immune responses. However, IFN-gamma can exert distinct effects in different persistent viral infections. The long-term overproduction of IFN-γ in retroviral infections, such as the human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), and human endogenous retroviruses (HERVs), resulting in inflammation, may cause neuronal damage. This review is provocative about the role of IFN-γ during persistent retroviral infections and its relationship with the causation of some neurological disorders that are important for public health.
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Abstract Since 2004, in Colombia, the detection of human T-cell lymphotropic virus type 1 and 2 (HTLV-1-2) has been recommended for organ donors and recipients. The prevention of HTLV-1 and 2 infection in recipients is important due to its relationship with lymphoproliferative and inflammatory diseases and opportunistic infections. The objective of this study was to describe the seroprevalence of HTLV-1 and 2 among organ donors and kidney transplant recipients between 2010 and 2017 in Colombia. Methods: this was a descriptive study which included 1979 organ donors and 3,311 kidney transplant recipients from the donation and transplant network from 2010 to 2017. The seroprevalence of HTLV-1 and 2 was calculated, and serological and demographic variables were described. Results: out of 1979 donors, detection of antibodies against HTLV-1 was performed in 92% (1820), with a seroprevalence of 0.2%; 50% of the cases were from the Pacific region (an endemic zone in Colombia). Ninety percent of the donors were examined for HTLV-2, with a seroprevalence of 0.2%. Of the 3311 kidney recipients between 2010 and 2017, only 44% were evaluated for HTLV-1 and 43% for HTLV-2. The seroprevalence for both viruses was 0.3%. Two of the HTLV-1 cases were positive for HLADRB1*01. Conclusions: the seroprevalence found in organ donors and kidney transplant recipients was similar to that previously reported in Colombia. Screening of all potential donors must be adhered to prevent transmission of this virus. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2001).
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Antecedentes: La aplasia medular es una enfermedad caracterizada por pancitopenia con médula ósea hipocelular. La mayor parte de estas son adquiridas pudiendo ser idiopáticas o secundarias al daño de la médula ósea producido por agentes físicos, químicos o infecciosos. El HTLV-1 es un retrovirus intracelular que se transmite por la lactancia materna prolongada, las relaciones sexuales y las transfusiones sanguíneas. Descripción del caso: Reportamos el caso de una mujer de 28 años que presentó petequias, gingivorragia y palidez generalizada. En sus exámenes se encontró pancitopenia severa, HTLV-1 positivo y en el aspirado de médula ósea, hipocelularidad marcada. Se administró antibióticos, antifúngicos, antivirales y agentes inmunosupresores con una evolución estacionaria. Conclusiones: La infección por HTLV-1 es frecuente en Perú; sin embargo, su asociación con aplasia medular es poco descrita. El trasplante de células madre hematopoyéticas es una alternativa de tratamiento en caso de no responder a la terapia inmunosupresora.
Background:Medullary aplasia is a disease characterized by pancytopenia with hypocellular bone marrow. Most of these are acquired and can be idiopathic or secondary to bone marrow damage produced by physical, chemical or infectious agents. HTLV-1 is an intracellular retrovirus that is transmitted by prolonged breastfeeding, sexual intercourse, and blood transfusions. Case description: We report the case of a 28-year-old woman who presented petechiae,gingivorrhagia,andgeneralizedpaleness.Inthelaboratory examination, severe pancytopenia was found, HTLV-1 positive, and in the bone marrow aspirate, marked hypocellularity. She received antibiotics, antifungals, antivirals, and immunosuppressive agents with a steady course. Conclusions:HTLV-1 infection is common in Peru; however, its association with medullary aplasia is poorly described. Hematopoietic stem-cell transplantation is an alternative treatment in case of failure to respond to immunosuppressive therapy.
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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.
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Movilidad en la CiudadRESUMEN
Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.
Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.
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Humanos , Masculino , Adulto , Persona de Mediana Edad , Virus Linfotrópico T Tipo 1 Humano/genética , Infecciones por HTLV-I/diagnóstico , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Linfocitos TRESUMEN
Summary The Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus with oncogenic properties, affects around ten to twenty million people worldwide. The most common disorders associated with HTLV-1 infection are T-cell leukemia/lymphoma (ALT) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Studies have reported other clinical manifestations in HTLV-1 seropositive patients, including inflammatory disorders, co-infections with opportunistic agents, and pulmonary diseases. Objective: Here, we aim to describe a cohort of juvenile patients with confirmed HTLV-1 infection that showed clinical manifestations other than neurological symptoms. Methodology and patients: Retrospective analysis of clinical data describing background and clinical findings of 12 juvenile patients with confirmed HTLV-1 infection, attended during January 2018 to February 2020 in a pediatric referral hospital in Cali, Colombia. Results: 11 out 12 patients were from Colombia´s Pacific coast, 10 suffered from significant nutritional deficiencies. Six exhibited dermatological findings, 3 compatible with infective dermatitis. None of the cases exhibited clinical or laboratory findings suggesting ALT or HAM/TPS. Eight patients had structural lung disease assessed by chest Computed Tomography (CT) scans; 4 of them tested positive for galactomannan antigen in bronchoalveolar fluid suggesting pulmonary aspergillosis, and 2 others exhibited a positive PCR testing for tuberculosis. Three patients were diagnosed with autoimmune disorders; 1 patient with Crohn´s Diseases, 1 case of autoimmune thrombocytopenic purpura, and a patient with Vogt-Koyanagi-Harada syndrome (non-granulomatous uveitis). Conclusions: There is a broad range of clinical manifestations in pediatric HTLV-1 patients, and the clinician should consider structural pulmonary disease, opportunistic co-infections and autoimmune disorders in the diagnostic algorithm.
Resumen El Virus Linfotrópico de células T humanas tipo 1 (HTLV-1), retrovirus con propiedades oncogénicas, afecta alrededor de 10-20 millones de personas mundialmente. Las manifestaciónes más comúnmente asociadas a HTLV-1 incluyen leucemia/linfoma de células T (ALT) y mielopatía asociada a HTLV-1/ paraparesia espástica tropical (HAM/TSP). Estudios han reportado otras manifestaciones clínicas en pacientes positivos para HTLV-1, incluyendo enfermedades inflamatorias, coinfecciones con gérmenes oportunistas y enfermedad pulmonar. Objetivo: es describir clínicamente una cohorte de pacientes pediátricos con infección por HTLV-1 confirmada que presentan manifestaciones clínicas diferentes a síntomas neurológicos. Metogolodía y pacientes: Análisis retrospectivo de historia clínica describiendo procedencia y hallazgos clínicos en 12 pacientes con infección por HTLV-1 confirmada, atendidos durante el periodo de Enero de 2018 a Febrero de 2020 en un hospital pediátrico de referencia en Cali, Colombia. Resultados: Once de 12 pacientes procedían de la costa Pacífica Colombiana, 10 con deficiencias nutricionales significativas. Seis mostraron compromiso dermatológico, 3 compatibles con dermatitis infectiva. Ningún paciente presentó hallazgos clínicos o paraclínicos sugestivos de ALT o HAM/TPS. Ocho pacientes presentaron enfermedad pulmonar estructural evidenciada por TAC de tórax; 4 de ellos con antígeno galactomanan positivo en lavado broncoalveolar, sugiriendo aspergilosis pulmonar, y otros 2 resultaron con PCR positiva para tuberculosis. Tres pacientes presentaron enfermedades autoinmunes concomitantes: uno con Enfermedad de Crohn, uno con Púrpura Trombocitopénica Autoinmune, y un paciente con Síndrome de Vogt-Koyanagi-Harada. Conclusiones: Existe un amplio rango de manifestaciones clínicas en pacientes pediátricos con HTLV-1, considerando enfermedad pulmonar estructural, coinfecciones oportunistas y enfermedades autoinmunes dentro del algoritmo diagnóstico.
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Humanos , Lactante , Preescolar , Niño , Adolescente , Virus , Virus Linfotrópico T Tipo 1 Humano , Infecciones , Paraparesia Espástica Tropical , Leucemia , Enfermedad de Crohn , Costas (Litoral) , Síntomas Concomitantes , Síndrome Uveomeningoencefálico , Púrpura Trombocitopénica Idiopática , Desnutrición , Dermatitis , Aspergilosis Pulmonar , Enfermedades PulmonaresRESUMEN
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)
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Humanos , Paraparesia Espástica Tropical , Modalidades de Fisioterapia , Fatiga , Ejercicio Físico , Virus Linfotrópico T Tipo 1 HumanoRESUMEN
BACKGROUND@#Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up.@*METHODS@#Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway.@*RESULTS@#HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]).@*CONCLUSION@#Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de las Arterias Carótidas/virología , Estudios Transversales , Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano/fisiología , Hipertensión/virología , Japón/epidemiologíaRESUMEN
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.
RESUMEN
ABSTRACT Infection by human T-cell lymphotropic virus type 1 (HTLV-1) occurs in lymphocytes, which travel throughout the body, thus affecting several target organs and causing varied clinical outcomes, particularly in populations that are underserved and do not have access to healthcare. However, the mechanism of pathogenesis is not yet fully understood. The TAX and HTLV-1 basic leucine zipper factor (HBZ) proteins maintain viral persistence and affect pathogenesis through cell proliferation and immune and inflammatory responses that accompany each clinical manifestation. TAX expression leads to inhibition of transcription error control, OX40 overexpression, and cell proliferation in adult T-cell leukemia (ATL). OX40 levels are elevated in the central nervous system (CNS), and the expression of TAX in the CNS causes neuronal damage and loss of immune reactivity among patients with HTLV-1-associated myelopathy (HAM). HBZ reduces viral replication and suppresses the immune response. Its cell compartmentalization has been associated with the pathogenesis of HAM (cytoplasmic localization) and ATL (nuclear localization). TAX and HBZ seem to act antagonistically in immune responses, affecting the pathogenesis of HTLV-1 infection. The progression from HTLV-1 infection to disease is a consequence of HTLV-1 replication in CD4+ T and CD8+ T lymphocytes and the imbalance between proinflammatory and anti-inflammatory cytokines. The compartmentalization of HBZ suggests that this protein may be an additional tool for assessing immune and inflammatory responses, in addition to those already recognized as potential biomarkers associated with progression from infection to disease (including human leukocyte antigen (HLA), killer immunoglobulin-like receptors (KIR), interleukin (IL)-6, IL-10, IL-28, Fas, Fas ligand, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and mannose-binding lectin).