Infección por virus linfotrópico de células T humanas: Síndrome de Sezary asociado a paraparesia espástica tropical apropósito de un caso / Human T-cell lymphotropic virus infection: Sezary syndromeassociated with tropical spastic paraparesis: a case report

El virus linfotrópico de células T humanas tipo 1(HTLV-1, por sus siglas en inglés) es parte de la familia de los Retroviridae, perteneciente al género de los Delta retrovirus, está compuesto por una envoltura lipídica, obtenida de la célula huésped, en la superficie expresa proteínas transmembrana que le permite el anclaje e internalización por endocitosis al citoplasma celular. En su interior cuenta con una hebra de ARN de cadena simple en sentido positivo, además de las enzimas integrasa y transcriptasa inversa que forman la núcleo cápside icosaédrica. El virus linfotrópico de células T humanas está ampliamente distribuido a nivel mundial. Existen múltiples vías de transmisión (Transmisión vertical, interacciones sexuales, transfusiones sanguíneas, uso de drogas ilícitas endovenosas y el contacto de fluidos cargados de viriones con las mucosas). El 90% de los pacientes expuestos no desarrollaran síntomas, pero existe un 10% de los pacientes que desarrollaran el cuadro clínico. El HTLV-1 se asocia a dos cuadros clínicos bien establecidos: la paraparesia espática tropical y el linfoma cutáneo-T-leucemia de células T. Al ser inusual, presentándose en 1 de cada 100.000 habitantes, se discute el caso de una paciente femenina de 63 años de edad, con antecedentes de acalasia corregida quirúrgicamente, quien consulta con cuadro clínico de 2 meses de duración, caracterizado por debilidad progresiva simétrica en miembros inferiores que le impide la deambulación, incontinencia urinaria, lesiones cutáneas extensas y la presencia de hiperleucocitosis con más de 20% de blastos en sangre periférica, se realiza inmunofenotipo expresando que el 85% de linfocito T neoplásicos, resultando en leucemia de células T o síndrome de Sezary, posteriormente se confirma el diagnóstico al realizar Elisa de cuarta generación positivo para HTLV-1(AU)

The human T-cell lymphotropic virus is part of the Retroviridae family, belonging to the Delta retrovirus genus, thisvirus is composed of a lipid envelope, obtained from the hos tcell, on the surface it expresses transmembrane proteins that allow it to anchor and internalization by endocytosis into the cell cytoplasm. Inside it has a single-stranded RNA strand the positive direction, in addition to the enzymes integrase andreverse transcriptase that form the icosahedral nucleo capsid. Human T-cell T-cell lymphotrophic virus is widely distribute dworldwide. There are multiple routes of transmission (vertical transmission, sexual interactions, blood transfusions, use of intravenous illicit drugs and contact of virion-laden fluidswith mucous membranes). 90% of exposed patients will not develop symptoms, but there is 10% of patients who will develop the clinical picture, HTLV-1 is associated with twowell-established clinical pictures: tropical spastic paraplegia and cutaneous T-cell lymphoma. T-cell leukemia. As it is unusual, occurring in 1 out of every 100,000 inhabitants, the caseof a 63-year-old female patient with a history of surgically corrected achalasia is discussed, who consults with a clinical picture of 2 months duration, characterized due to progressive symmetrical weakness in the lower limbs that prevent walking, urinary incontinence, extensive skin lesions and the presence of hyperleukocytosis with more than 20% of blasts in peripheralblood, an immunophenotype is performed, expressing that 85% of neoplastic T lymphocytes, resulting in (T-cell leukemia) Sesary syndrome, diagnosis is later confirmed by performing afourth generation Elisa positive for HT LV-1(AU)

Metaanálisis de la validez del inmunodiagnóstico del virus linfotrópico de células T humanas i/ii en bancos de sangre, 2000-2018 / Meta-analysis regarding the validity of the immunodiagnosis of human T-cell lymphotropic virus I/II in blood banks, 2000-2018 / Meta-análise da validade do imunodiagnóstico do vírus linfotrópico de células t humanas I/II em bancos de sangue, 2000-2018

Resumen Objetivo: Evaluar la validez del inmunodiagnóstico del htlv i/ii en bancos de sangre, con base en estudios publicados en la literatura científica. Metodología: Se efectuó un metaanálisis de pruebas diagnósticas siguiendo la guía prisma y las recomendaciones de Cochrane. Se evaluó la calidad metodológica con quadas y se garantizó la reproducibilidad y la exhaustividad. Se realizó también un análisis de efectos aleatorios para la sensibilidad, la especificidad, los cocientes de probabilidad, la razón de momios diagnóstica y la curva característica operativa del receptor (roc) con sus intervalos de confianza (ic) del 95 %. Resultados: Se tamizaron 4604 estudios, de los cuales solo tres cumplieron el protocolo. Se evaluaron 548 infectados con htlv i/ii y 6643 sanos. El inmunodiagnóstico de htlv i/ii presentó una sensibilidad del 99 % (ic95 % = 98,0-99,0), especificidad del 100 % (ic95 % = 99,9-100), cocientes de probabilidad positivo de 315,8 (ic95 % = 128,2-778,5) y negativo de 0,02 (ic95 % = 0,01-0,04), razón de momios diagnóstica de 24373 (ic95 % = 6864-86545) y área bajo la curva roc del 99,9 %. Conclusión: Se dispone de pocos estudios en este campo del inmunodiagnóstico htlv i/ii. El elevado número de sujetos analizados evidenció alta validez del inmunodiagnóstico, lo que resulta determinante para garantizar la inocuidad de las unidades de sangre, la detección de portadores asintomáticos, la disminución de la transmisión y el inicio de tratamiento.

Abstract Objective: To evaluate the validity of the immunodiagnosis of htlv i/ii in blood banks, based on studies published in the scientific literature. Methodology: A meta-analysis of diagnostic tests was carried out following the PRISMA guidelines and Cochrane recommendations. The methodological quality was evaluated with QUADAS, and reproducibility and completeness were guaranteed. A random effects analysis was also performed with respect to sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curve (ROC) with their 95 % confidence intervals (CI). Results: 4,604 studies were screened, of which only three complied with the protocol. 548 subjects infected with HTLV I/II and 6,643 healthy subjects were evaluated. The immunodiagnosis of HTLV I/II had a sensitivity of 99 % (95 % CI = 98.0-99.0), a specificity of 100 % (95 % CI = 99.9-100), a positive likelihood ratio of 315.8 (95 % CI = 128.2-778.5) and a negative likelihood ratio of 0.02 (95 % CI = 0.01-0.04), a diagnostic odds ratio of 24,373 (95 % CI = 6,864-86,545), and an area under the ROC curve of 99.9 %. Conclusion: Few studies are available in the field of HTLV I/II immunodiagnosis. The high number of subjects analyzed showed high validity of the immunodiagnosis, which is decisive to guarantee the safety of the blood units, the detection of asymptomatic carriers, the decrease in transmission, and the start of treatment.

Resumo Objetivo: Avaliar a validade do imunodiagnóstico do HTLV I/II nos bancos de sangue, baseados nos estudos publicados na literatura científica. Metodologia: Foi realizada uma meta-análise de testes diagnósticos seguindo a guia PRISMA e as recomendações de Cochrane. Foi avaliada a qualidade metodológica com QUADAS e garantiu-se a reprodutibilidade e a integridade. Realizou-se também uma análise de efeitos aleatórios para a sensibilidade, a especificidade, os quocientes de probabilidade, a razão de probabilidade diagnóstica e a Curva Característica de Operação do Receptor (Curva ROC) com seus Intervalos de Confiança (IC) de 95%. Resultados: Foram selecionados 4604 estudos, dos quais somente 3 cumpriram com o protocolo. Foram avaliados 548 infectados com o vírus HTLV I/II e 6.643 saudáveis. O imunodiagnóstico de HTLV I/II apresentou uma sensibilidade de 99% (IC95% = 98,0-99,0), especificidade de 100% (IC95%= 99,9-100), quocientes de probalidade positiva de 315,8 (IC95% = 128,2-778,5) e negativo de 0,02 (IC95% = 0,01-0,04), razão de probabilidade diagnóstica de 24373 (IC95% = 6864-86545) e área sob a curva ROC de 99,9%. Conclusão: São poucos os estudos disponíveis neste campo do imunodiagnóstico HTLV I/II. O elevado número de pessoas analisadas evidenciou alta validade do imunodiagnóstico, o que é decisivo para garantir a inocuidade das unidades de sangue, a detecção de portadores assintomáticos, a diminuição da transmissão e o início do tratamento.

Uso da eletromiografia de superfície na resultância do treinamento muscular inspiratório com carga linear em portadores do vírus linfotrópico humano tipo 1 / Use of surface electromyography in results of inspiratory muscle training with linear load in patients with type 1 human lymphotropic virus

Este estudo visa avaliar por eletromiografia de superfície o comportamento dos músculos inspiratórios no treinamento muscular em voluntários com vírus linfotrópico de célula T humana do tipo 1. Trata-se de um ensaio clínico. Sete voluntários, com idade 58,85 ± 7,2) anos, realizaram treinamento muscular inspiratório domiciliar por 4 semanas, 3 vezes por semana, 30 minutos diários por meio de incentivador de carga linear. Para avaliação utilizou-se os dados de pressão inspiratória máxima e os dados da eletromiografia de superfície nas fases pré (T0), segunda semana (T2) e após a quarta semana (T4) de treinamento. Observou-se aumento progressivo da força muscular inspiratória de T0 a T4 (p = 0,007), assim como, aumento do recrutamento das unidades motoras pela análise da amplitude do sinal eletromiográfico, sendo mais evidente para o músculo esternocleidomastóideo (p = 0,12) em comparação ao músculo diafragma (p = 0,6). Verificou-se que no decurso do treinamento muscular ocorreu melhora significativa da força muscular inspiratória com maior recrutamento das fibras musculares dos músculos analisados na amostra. (AU)

This study aimed to evaluate by surface electromyography the behavior of inspiratory muscles in the muscle training of volunteers with human T-cell lymphotropic virus type 1. This was a clinical trial. Seven volunteers, 58,85 ± 7.21 years old, underwent inspiratory muscle training at home for 4 weeks, 3 times a week, 30 minutes daily by means of a linear load stimulator. The maximum inspiratory pressure data and the surface electromyography data were used for evaluation in the pre (T0), second week (T2) and after the fourth week (T4) training phases. There was a progressive increase in inspiratory muscle strength from T0 to T4 (p = 0.007), as well as an increase in the recruitment of motor units by analyzing the amplitude of the electromyographic signal, being more evident for the sternocleidomastoid muscle (p = 0.12) in comparison to the diaphragm muscle (p = 0.6). During the muscle training inspiratory muscle strength improves with greater recruitment of muscle fibers from the muscles analyzed in the sample. (AU)

Specificity of HTLV screening tests and its impact on health care program costs: The perspective of antenatal screening in Brazil

Abstract INTRODUCTION: Brazil ranks first in the number of HTLV-1/-2-infected individuals worldwide. The high morbidity and mortality of HTLV-1-associated diseases, especially following infection in infancy, requires strong action to reduce vertical transmission. METHODS: To facilitate the appraisal of the implementation of the HTLV antenatal screening program by the Brazilian Ministry of Health, we determined the costs in distinct scenarios according to HTLV seroprevalence, specificity of the screening test, and type of confirmatory test. RESULTS: HTLV antenatal screening would cost R$ 55,777,012-R$ 77,082,123/year. Screening assays with high specificity reduce the need and cost of confirmatory assays by up to 25%. CONCLUSIONS: Careful selection of the screening assay is required to optimize the program.

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.

Brazilian protocol for sexually transmitted infections 2020: human T-cell lymphotropic virus (HTLV) infection

Abstract This article addresses the Human T-lymphotropic virus (HTLV). This subject comprises the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. HTLV-1/2 infection is a public health problem globally, and Brazil has the largest number of individuals living with the virus. HTLV-1 causes several clinical manifestations of neoplasm (adult T-cell leukemia/lymphoma) and inflammatory nature, such as HTLV-1-associated myelopathy and other manifestations such as uveitis, arthritis, and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health authorities professionals regarding viral transmission, diagnosis, treatment, and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Quality of life, risk behaviors and depression among carriers of hepatitis C virus and human T-cell lymphotropic virus type 1: a comparative study

Abstract Human T-cell lymphotropic virus type 1 (HTLV-1) has low prevalence rates, but is endemic in some regions of the world. It is usually a chronic asymptomatic infection, but it can be associated with serious neurologic and urinary conditions. Hepatitis C virus (HCV) is broadly spread out worldwide. The majority of these infections have a chronic course that may progress to cirrhosis and hepatocellular carcinoma. Objectives: To compare sociodemographic and mental health (risk behaviors, depression, and suicide) aspects, and quality of life among patients with HCV or HTLV-1. Methods: Observational, comparative and cross-sectional study involving outpatients with HCV or HLTV-1 infection. Sociodemographic characteristics, risk behaviors and quality of life were assessed through the questionnaires Mini International Neuropsychiatric Interview - MINI Plus (depression and suicide) and Medical Outcomes Study 36-Item Short-Form Health Survey (quality of life). Univariate and multivariate statistical analyses (hierarchical logistic regression) were conducted. Results: 143 individuals with HCV and 113 individuals with HTLV-1 infection were included. Males were predominant in the HCV group (68.8%) and females in the HTLV-1 group (71.7%). The frequency of risk behaviors (sexual and drug use) was greater in those with HCV (p < 0.05). A past depressive episode was more common in the HTLV-1 group (p = 0.037). Quality of life was significantly worse in the physical functioning, vitality, mental health, and social functioning domains in those with HTLV-1 (p < 0.05). HTLV-1 infection remained independently associated with worse quality of life in multivariate analysis. Conclusions: Risk behaviors are frequent among those infected with HCV. Additionally, despite HTLV-1 being considered an infection with low morbidity, issues related to mental health (depressive episode) and decreased quality of life are relevant.

Comparison of the Effectiveness in the Application of Competitive and Noncompetitive Internal Control for the Laboratory Developed Polymerase Chain Reaction / 대한수혈학회지

BACKGROUND: A nucleic acid amplification test was adopted to detect transfusion-transmitted infectious agents. In the case of HTLV, however, there was no internal control (IC) because the laboratory developed polymerase chain reaction (laboratory-developed PCR) was used. In this study, noncompetitive IC was constructed for the laboratory-developed PCR of HTLV and the effectiveness was compared with the competitive test that was constructed in a previous study. METHODS: As a competitive IC, plasmid DNA, including the primer recognition sequence for the amplification of the HTLV pX region, was constructed. As a noncompetitive IC, an additional primer was constructed for the amplification of the housekeeping gene, the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. The performance of the competitive and noncompetitive IC was verified and compared using 10 HTLV positive samples and 10 negative samples. In addition, the detection limits in the assay adopting competitive IC and noncompetitive IC were compared. RESULTS: In the case of competitive IC applications, all 10 positive samples were positive and all 10 negative samples were negative. In the case of noncompetitive IC applications, however, one positive sample was not detected. The detection limit of the assay using competitive IC was 100 pg and that of the assay using noncompetitive IC was 1 ng. CONCLUSION: Although the manufacturing processes is not required using noncompetitive IC, the adoption of competitive IC is more effective to ensure the assay results because the ability of detection of the assay adopting competitive IC was better than that using noncompetitive IC.

Adult T-cell leukemia/lymphoma and acquired immunodeficiency syndrome - CD4+ T-cell malignancy in CD4+ T-cell deficient status: A paradox

CD4 counts along with viral loads are important parameters in the monitoring of human immunodeficiency virus (HIV) infection. Human T-cell lymphotropic virus type I (HTLV-I) is known to be an etiological agent for adult T-cell leukemia/lymphoma (ATLL). Coinfection of HTLV-I and HIV is well known in regions with high seroprevalence, and there is no published data in the Indian scenario. We present an interesting case of occurrence of CD4+ T-cell proliferation in a known beta thalassemia major with acquired HIV seropositivity accompanied by simultaneously increasing CD4+ counts and viral loads. Further workup revealed ATLL with an underlying HTLV infection.

Prevalência de infecção pelos vírus linfotrópicos de células T humanas dos tipos 1 e 2 (HTLV-1 e HTLV-2) e vírus da imunodificiência humana do tipo 1 (HIV-1) em população infectada pelos vírus da hepatite B (HBV) e hepatite C (HCV)

Os vírus linfotrópicos de células T humanas dos tipos 1 (HTLV-1) e 2 (HTLV2),assim como o vírus da imunodeficiência humana (HIV) e os vírus dashepatites B (HBV) e C (HCV) compartilham vias de transmissão, portantocoinfecções por estes vírus podem acontecer e alterar o curso das doençasa eles relacionadas. O presente estudo avaliou a prevalência de infecção porHTLV-1/2 em população com hepatite B e C, infectada ou não pelo HIV, e oimpacto das coinfecções na viremia HBV e HCV. O estudo foi realizado em1.244 amostras de plasma/soro enviadas ao Instituto Adolfo Lutz de SãoPaulo para determinação de carga viral (CV) de HBV e HCV: 622 depacientes com HBV (G1, 327 homens e 295 mulheres, média de idade 45,8anos) e 622 de pacientes com HCV (G2, 343 homens e 279 mulheres, médiade idade de 50,8 anos). A triagem de HTLV-1/2 foi realizada por ensaioimunoenzimático (EIA HTLV-I/II, Gold ELISA, REM) e confirmadas porWestern Blot (HTLV BLOT 2.4, MP Biomedicals) e imunoensaio de linha(INNO-LIA HTLV-I/II, Fujirebio). A pesquisa de infecção por HIV foi realizadapor teste imunocromatográfico (kit Rapid Check HIV 1 e 2, NDI, UniversidadeFederal do Espírito Santo, Brasil) seguido do EIA (GS HIV-1/HIV-2 Plus OEIA, Bio-Rad). A infecção por HTLV-1 foi confirmada em 25 amostras (cincono G1 e 20 no G2)...

The human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) aswell as the human immunodeficiency virus (HIV) and the hepatitis B virus(HBV) and hepatitis C virus (HCV) share routes of virus transmission; thusco-infections with such viruses can occur and alter the course of subsequentdiseases. The present study aimed at evaluating the prevalence of HTLV-1/-2 in blood samples of individuals with hepatitis B and C, infected or not byHIV, and the impact of co-infections on the HBV and HCV viremia. The studywas conducted with 1,244 plasma/serum samples sent to Instituto AdolfoLutz of São Paulo for measuring HCV and HBV viral load (VL): 622 fromHBV-infected patients (G1, 327 male and 295 female, median age 45.8years), and 622 from HCV-infected patients (G2, 343 male and 279 female,median age 50.8 years). HTLV-1/-2 antibodies were screened by enzymeimmunoassay (EIA, HTLV-I/II, Gold ELISA, REM), and confirmed by Westernblot (HTLV BLOT 2.4, MP Biomedicals), and line immunoassay (INNO-LIAHTLV-I/II, Fujirebio). The HIV infection was detected byimmunochromatographic assay (Rapid Check HIV 1 e 2, NDI, UniversidadeFederal do Espírito Santo, Brasil) and by EIA (GS HIV-1/HIV-2 Plus O EIA,Bio-Rad). HTLV-1 was confirmed in 25 samples (5 in G1 and 20 in G2)...

Algorithm for dry eye disease diagnosis in individuals infected with human T-cell lymphotropic virus type 1 / Algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com vírus linfotrópico de células-T humanas tipo 1

ABSTRACT Purpose: To evaluate the accuracy of lacrimal film tests and propose an algorithm for the diagnosis of dry eye disease in individuals infected with human T-cell lymphotropic virus type 1. Methods: Ninety-six patients infected with human T-cell lymphotropic virus type 1 were enrolled in the study. To assess clinical complaints, patients completed the Ocular Surface Disease Index questionnaire. To evaluate lacrimal film quality, patients underwent the tear breakup time test, Schirmer I test, and Rose Bengal staining. Dry eye disease was diagnosed when at least two of the three test results were abnormal. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of the questionnaire as well as of each test alone and combined in parallel and in series were determined. Results: The most sensitive test was the tear breakup time test (98%), whereas the most specific was the Schirmer I test (100%). Rose Bengal staining had the highest overall accuracy (88.64%), whereas the Ocular Surface Disease Index had the lowest overall accuracy (62.65%). The tear breakup time test, Schirmer I test, and Ocular Surface Disease Index combined in parallel showed increased sensitivity and decreased specificity for all tests. In contrast, when combined in series, these tests demonstrated increased specificity and decreased sensitivity. Conclusion: This study shows the need to use multiple tests to evaluate tear film quality and include a symptom questionnaire as part of the diagnostic algorithm for dry eye disease.

RESUMO Objetivo: Avaliar a precisão da propedêutica do filme lacrimal e propor um algoritmo para o diagnóstico da doença do olho seco em indivíduos infectados com Vírus linfotrópico de células-T humanas tipo 1. Métodos: Noventa e seis pacientes infectados com o vírus linfotrópico de células T humana tipo 1 foram incluídos no estudo. Para avaliar sintomatologia, os pacientes responderam o questionário Índice para Doenças da Superfície Ocular. A fim de avaliar a qualidade do filme lacrimal, os pacientes foram submetidos ao teste de ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala. A doença do olho seco foi diagnosticada quando, pelo menos, dois dos testes ruptura do filme lacrimal, teste de Schirmer I e coloração com Rosa Bengala) eram anormais. Foram determinados sensibilidade, especificidade, valor preditivo positivo e negativo e acurácia do questionário e de cada teste sozinho e combinados em paralelo e em série. Resultados: O teste de ruptura do filme lacrimal foi o mais sensível (98%) e o teste de Schirmer I foi o mais específico (100%). A maior acurácia foi encontrada no teste de coloração com Rosa Bengala (88,64%), enquanto sintomas avaliados usando o questionário Índice para Doenças da Superfície Ocular teve a menor acurácia geral (62,65%). O teste de ruptura do filme lacrimal, teste de Schirmer I e Questionário de Doença da Superfície Ocular quando combinados em paralelo mostraram um aumento da sensibilidade e uma diminuição na especificidade de todos os testes. Por outro lado, combinados em série, teste de ruptura do filme lacrimal, Schirmer I e questionário Índice para Doenças da Superfície Ocular tiveram um aumento na especificidade e sensibilidade diminuída. Conclusão: Este estudo apontou a necessidade de utilizar mais do que um teste para avaliar a qualidade do filme lacrimal, bem como utilizar um questionário de sintomas como parte do algoritmo de diagnóstico para doença do olho seco.

Factors associated with pain in individuals infected by human T-cell lymphotropic virus type 1 (HTLV-1)

Abstract Introduction Despite the high prevalence of chronic pain in individuals infected with HTLV-1, predictive and protective factors for its development are still unclear. Objective To identify factors associated with chronic pain in individuals with HTLV-1. Methods This cross-sectional study was conducted in a reference center for treatment of patients infected with HTLV-1 in Salvador, Bahia, Brazil. The study included individuals infected with HTLV-1, over 18 years, and excluded those with difficulty to respond the pain protocol. Data on sociodemographic, health behavior, and clinical characteristics were collected in a standardized way. The prevalence ratio (PR) of pain is described, as well as the factors independently associated with the presence of pain, which were assessed by multiple logistic regression. Results A total of 142 individuals were included in the study, mostly female (62.7%), aged 20–64 years (73.2%), married (61.3%), with less than eight years of education (54.2%), and with a steady income (79.6%). Multivariate analysis showed that being symptomatic for HTLV-1 – sensory manifestations, erectile dysfunction, overactive bladder, and/or HAM/TSP (PR = 1.21, 95% CI: 1.05 to 1.38), self-medication (PR = 1.29, 95% CI: 1.08–1.53), physiotherapy (PR = 1.15, 95% CI: 1.02–1.28), and depression (PR = 1.14, 95% CI: 1.01–1.29) were associated with an increased likelihood of presenting pain. On the other hand, physical activity (PR = 0.79, 95% CI: 0.67–0.93) and religious practice (PR = 0.83, 95% CI: 0.72–0.95) were associated with a decreased likelihood of having pain. Conclusion The use of self-medication, physiotherapy and the presence of depression are independently associated with neurological symptoms in HTLV-1 infected patients. Religious practice and physical activity are both protective for the development of pain.

Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.

Adult T-cell leukemia/lymphoma / Leucemia/linfoma de células T do adulto

Summary Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Twenty million people are believed to be infected throughout the world, mostly in Japan, Africa, the Caribbean, and South America, particularly in Brazil and Peru. ATL affects about 5% of infected individuals and is classified in the following clinical forms: acute, lymphoma, primary cutaneous tumoral, chronic (favorable and unfavorable), and smoldering (leukemic and non-leukemic). Although it is considered an aggressive disease, there are cases with a long progression. We emphasize the importance of clinical classification as an indispensable element for evaluating prognosis and appropriate therapeutic approach. Since several cases have been published in Brazil and this disease is still poorly known, we decided to make a review paper for dissemination of clinical, hematological and pathological aspects, diagnosis, and therapy. The best way to reduce the occurrence of ATL would be halting the transmission of the virus through breastfeeding.

Resumo A leucemia/linfoma de células T do adulto (LLcTA) é uma neoplasia de células T maduras CD4+ causada pelo vírus linfotrópico para células T humanas tipo 1 (HTLV-1). Acredita-se que existem cerca de 20 milhões de pessoas infectadas em todo o mundo, principalmente no Japão, na África, no Caribe e na América do Sul, particularmen te no Brasil e no Peru. A LLcTA acomete cerca de 5% dos indivíduos infectados e classifica-se nas seguintes formas clínicas: aguda, linfomatosa, tumoral primária de pele, crônica (favorável e desfavorável) e indolente (leucêmica e não leucêmica). Embora seja considerada uma doença agressiva, há casos com longa evolução. Salientamos a importância da classificação clínica como elemento im prescindível para avaliação do prognóstico e conduta terapêutica adequada. Como já foram publicados vários casos no Brasil e essa doença ainda é pouco conhecida, decidimos fazer um trabalho de revisão para divulgar os seus aspectos clínicos, hematológicos, anatomopatológi cos, diagnósticos e terapêuticos. O melhor meio de redu zir a ocorrência de LLcTA seria sustando a transmissão vertical do vírus pela amamentação.

Seroprevalencia de HTLV1/2 en donantes de sangre, Boyacá - Colombia, 2011-2013 / Seroprevalence 1/2 HTLV in blood donors in Boyacá - Colombia between 2011 and 2013

Introducción: El virus linfotrópico humano de células T es un retrovirus, se encuentra asociado al riesgo de presentar dermatitis infecciosa, uveítis, polimiositis, artropatías, paraparesia espástica tropical, linfoma de células T del adulto y mieloma. Una de las vías de transmisión del HTLV 1/2 es la transfusión sanguínea de unidades que contienen el virus. Para evitar la transmisión de la infección por este retrovirus, el tamizaje en muestras de donantes de sangre ha sido obligatorio en muchos países y más recientemente en Colombia. Objetivo: Reportar la seroprevalencia de virus HTLV 1/ 2 en donantes de sangre de Boyacá-Colombia entre los años 2011 a 2013. Materiales y Métodos: Estudio descriptivo retrospectivo, en el que se estableció la seroprevalencia de HTLV 1/2 en 48.782 donantes de sangre captados en el departamento de Boyacá por tres bancos de sangre, utilizando la técnica quimioluminiscencia y como pruebas confirmatorias la técnica de InmunoBlot. Resultados: De los donantes tamizados, el 0,23% (113/48.782) fueron serorreactivos (positivos en la prueba de quimioluminiscencia), el 0,16% (78/48.782) fueron negativos, un 0,04% (21/48.782) fueron indeterminados y el 0,03% (14/48.782) fueron seropositivos por la técnica de InmunoBlot. Los donantes seropositivos correspondieron según el sexo a 0,016% (8/48.782) mujeres y 0,012% (6/48.782) a hombres. Conclusión: La prevalencia de HTLV 1/2 fue de 0,03%, similar a la de la mayoría de países que cuentan con reporte de esta determinación en donantes de sangre. Los datos generados en el estudio son los primeros reportados para Boyacá y aportan a la epidemiología del virus a nivel nacional.

Introduction: The Human T-cell lymphotropic virus is a retrovirus found to be associated with risks of infectious dermatitis, uveitis, polymyositis, arthropathies, tropical spastic paraparesis, myeloma and T-cell lymphoma. One of the means of transmission of HTLV 1/2 is the transfusion of blood units contaminated by the virus. To prevent this kind of transmission, blood donor screening has recently become a standard in Colombia and in many other countries. Objective: To report the seroprevalence of HTLV 1/2 virus in blood donors from Boyacá between 2011 and 2013. Materials and Methods: A retrospective descriptive study was performed, in which the seroprevalence of HTLV 1/2 was established in 48,782 blood donors from three blood banks in the department of Boyacá by using both chemiluminescence and western blot techniques. Results: From the screened donors, 0.23% (113 / 48,782) were seroreactive (chemiluminescence positive), 0.16% (78 / 48,782) were negative, 0.04% (21 / 48,782) were undefined and 0.03% (14 / 48,782) were seropositive by western blot. Concerning gender, seropositive donors were 0.016% (8/48,782) female and 0.012% (6 / 48,782) male. Conclusion: The prevalence of HTLV 1/2 was 0.03% which is similar to what has been found in most of the countries. The data generated in this study is the first of this kind available for Boyacá and will likely contribute to the virus epidemiology at the national level.

Perfil clínico-epidemiológico de pacientes infectados pelo HTLV-1 em Belém/Pará / Clinical-epidemiological profile of HTLV-1 infected patients in Belém, Pará state, Brazil

ResumoObjetivoInvestigar o perfil clínico-epidemiológico de pacientes portadores do HTLV-1 em Belém, no Estado do Pará, Brasil, descrevendo as características de indivíduos infectados e atendidos no Laboratório de Clínica e Epidemiologia de Doenças Endêmicas (LCEDE) do Núcleo de Medicina Tropical (NMT) da Universidade Federal do Pará (UFPA).MetodologiaFoi um estudo descritivo de corte transversal, com coleta em prontuários de pacientes infectados pelo HTLV-1, matriculados no LCEDE do NMT da UFPA entre os anos 2000 a 2012. Foi aplicada a análise descritiva pelo programa Epi Info 3.2.5.ResultadosDos 182 prontuários, 35,2% eram do sexo masculino, e 64,8%, do sexo feminino. Houve predomínio de indivíduos casados (47,8%). A maioria (73,6%) tinha procedência do município de Belém-PA. Dentre os pacientes sintomáticos, 51% apresentavam sintomas neurológicos, 21%, queixas dermatológicas, 18%, queixas reumatológicas, e 10%, queixas autonômicas. Com relação aos pacientes com sintomas neurológicos, 16 (39,0%) foram diagnosticados com PET/MAH.ConclusõesHouve o predomínio do sexo feminino, na faixa etária entre 40 e 49 anos, casado, trabalho informal, procedentes de Belém, com queixas neurológicas e com retorno regular as consultas médicas.

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

Sexual transmission of human T-cell lymphotropic virus type 1

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more efficiently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2), and chancroid. Other sexually transmitted diseases might result in the recruitment of inflammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are significantly higher from men to women than women to men.

Sulfated fucan from marine alga inhibits HeLa cells infection by HTLV-1 free particles: semi-quantitative analysis

A sulfated fucan from Laminaria abyssalis marine alga prevented the interaction of HTLV-1 particles, purified from the MT-2 cell line, with HeLa cells. The infection obtained using a concentrated virus suspension was detected only by amplification of the newly synthesized HTLV-1 proviral cDNA by the nested-polymerase chain reaction (PCR). The sulfated polysaccharide was not toxic to the cells at a concentration of 100 µg/mL and prevented infection by the viral particles when added to the cell monolayers. The proviral cDNA was only detected when the sulfated polysaccharide was added to the cells three hours post-infection, indicating that the inhibitory activity occurred in the initial stages of virus-cell interaction. Our results demonstrate, for the first time, the ability of a sulfated fucan from marine algae to inhibit virus transmission through free virus particles.

Seroprevalencia del virus linfotrópico humano de células T tipo 1 (HTLV-1) en pacientes con tiroiditis autoinmune / Human T cell lymphotropic virus type 1 (HTLV-1) seroprevalence among out-patients with autoimmune thyroiditis

Objetivo: Describir la seroprevalencia de infección por HTLV-1 en pacientes con tiroiditis autoinmune. Material y Métodos: Estudio transversal realizado en pacientes con tiroiditis autoinmune que acudieron al consultorio de Endocrinología del Hospital Nacional Cayetano Heredia entre octubre del 2008 y enero del 2010. Se usó un cuestionario estructurado para obtener datos epidemiológicos y clínicos, paralelamente, se revisaron las historias clínicas para obtener datos de laboratorio. A los participantes se les tomó una muestra de sangre para el diagnóstico de HTLV-1 mediante prueba de ELISA y confirmación por Western Blot, previa firma de consentimiento informado. Resultados: Durante el período de estudio, se atendieron 285 pacientes con tiroiditis autoinmune. Se incluyeron 145 pacientes(50,9%); la edad media fue 48,1 ± 15 años y 135 (93,1%) fueron de sexo femenino. Tres pacientes tuvieron infección por HTLV-1, con una prevalencia estimada de 2,1% (IC 95%: 0-4,4%). Los seropositivos fueron de sexo femenino y tuvieron el diagnóstico de Enfermedad de Graves hipertiroidea. La frecuencia de infección por HTLV-1 en este grupo fue de 5% (3/60); IC 95%: 0-11%. No se encontró diferencia significativa entre los pacientes HTLV-1 positivos y negativos en cuanto a características demográficas, clínicas y de laboratorio. Conclusión: La prevalencia de infección por HTLV-1 en los pacientes con tiroiditis autoinmune fue similar a la prevalencia estimada para la población peruana en general.

Objective: To describe the seroprevalence of human T-cell lymphotropic virus type 1 (HTLV-1) infection among patients with autoimmune thyroiditis diagnosis. Material and Methods: Cross-sectional study including subjects with autoimmune thyroiditis at the outpatient Endocrinology unit of the Hospital Nacional Cayetano Heredia from October 2008 to January 2010. A structured questionnaire was used to get epidemiologic and clinic data; and hospital registries were reviewed to determine laboratory data. Participants were tested for HTLV-1 using Enzyme-Linked Immunosorbent Assay and Western blot confirmation. All participant provided informed consent. Results: During the study period, 285 subjects with autoimmune thyroiditis were attended at the Endocrinology Outpatient Service. We included 145 (50.9%); their mean age was 48,1±15 years and 135 (93.1%) were female. Three were HTLV-1 positive, with estimated prevalence of 2.1% (95% CI: 0-4.4%). All seropositive patients were women andhad Graveæs disease. The frequency of HTLV-1 infection in this group was 5% (3/60); 95% CI: 0-11%. Non significant differences for demographic, clinical and laboratory characteristics between the HTLV -1 seropositive and seronegative patients were founded. Conclusions: The seroprevalence of HTLV-1 infection among outpatients with autoimmune thyroiditis was similar to that estimated for the peruvian general population.

Mielopatia associada ao HTLV-1: análise clínico-epidemiológica em uma série de casos de 10 anos / HTLV-1 associated myelopathy: clinical and epidemiological profile in a 10-year case series study

INTRODUÇÃO: A mielopatia associada ao retrovírus HTLV-1 (HAM/TSP) é uma doença progressiva e incapacitante. O objetivo deste trabalho é determinar características clínico-epidemiológicas de pacientes com HAM/TSP. MÉTODOS: Série de casos admitidos de 01/1998 a 12/ 2007, em hospital de reabilitação utilizando os critérios diagnósticos de HAM/TSP. RESULTADOS: Participaram 206 pacientes, dos quais, 67 por cento eram mulheres, com 53 anos de média de idade, nove anos de média de duração de doença. Os sintomas mais frequentes foram a diminuição da força em membros inferiores, espasticidade, dor, presença de bexiga neurogênica e a constipação intestinal. Os sinais neurológicos foram hiperreflexia, Babinsky, Hoffmann e neuropatia periférica. A presença de dor, de espasticidade muscular e de atrofia medular à ressonância nuclear magnética de medula espinhal foram associadas à duração da doença (p<0,05). CONCLUSÕES: A HAM/TSP é uma doença de curso incapacitante e progressiva, em que a dor é relatada precocemente, enquanto a atrofia medular torácica e a espasticidade surgem em fase mais tardia. Existem casos de HAM/TSP com provável transmissão do vírus por via vertical.

INTRODUCTION: Human T cell lymphotropic virus type 1 (HTLV-I) myelopathy (HAM/TSP) is a progressive disabling disorder. This work aimed to analyze clinical features and epidemiology in a sample of HAM/TSP. METHODS: All HTLV-1 infected patients with diagnostic criteria for HAM/TSP, consecutively admitted to the Sarah Hospital from 1998 to 2007, were included in the study. RESULTS: 206 patients (67 percent females; mean age: 53.8 years-old) were diagnosed with HAM/TSP. The mean time of evolution was 9.0 years. The most common neurological symptoms were chronic progressive spastic paraparesis, spasticity, pain, neurogenic bladder and neurogenic bowel. The neurological findings were hyperreflexia, Babinsky, Hoffman and peripheral neuropathy. Pain, spasticity and spinal cord atrophy, observed in MRI, were associated with time of disease (p<0.05). CONCLUSIONS: HAM/TSP is a very disabling disorder, in which pain is reported early, while spasticity and thoracic spinal cord atrophy appear in a later phase of the disease. Cases of HAM/TSP exist with a probable vertical viral transmission.