Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

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

Abstract INTRODUCTION: Human T-cell lymphotropic virus type 1 (HTLV-1)induces exaggerated Th1 responses, whereas atopy is associated with exacerbated Th2 responses. METHODS: Here, a cross-sectional study compared the prevalence of atopy in HTLV-1 carriers and HAM/TSP patients. It also compared the spontaneous cytokine production in HTLV-1-infected individuals. A retrospective cohort study evaluated the development of neurological manifestations in atopic and non-atopic carriers. RESULTS: Atopic HAM/TSP patients with high IFN-γ production exhibited higher IL-5 levels than non-atopic patients. Allergic rhinitis accelerated the development of Babinski signals and overactive bladders. CONCLUSIONS: Abnormal Th1 and Th2 responses coexist in HTLV-1-infected individuals and allergic diseases may worsen the clinical course of HTLV-1 infections.

Prolonged lymphocytosis as the first manifestation of Hodgkin-like adult T-cell leukemia/lymphoma

Abstract Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.

HTLV-1-associated infective dermatitis and probable HTLV-1- associated myelopathy in an adolescent female

Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (ID) is a chronic, severe and recurrent eczema occurring during childhood in patients vertically infected with HTLV-1. HTLV-1-associated myelopathy/tropical spastic paraparesia (HAM/ TSP) is slow and progressive. We report the case of an adolescent female from a non-endemic area for HTLV-1 who presents ID and, most likely, associated HAM/TSP.

Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T / Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma

Background: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). Aim: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. Material and Methods: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. Results: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). Conclusions: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.

Human T-cell leukaemia/lymphoma virus Type-1 associated myeloneuropathies: a caribbean perspective / Mieloneuropatías asociadas con el virus humano de células tipo 1 de la leucemia/linfoma: una perspectiva caribeña

This review follows the contributions of researchers from the Caribbean in improving the understanding of the disease mechanisms, clinical features and aetiology of neurological syndromes manifesting as diseases of the spinal cord and peripheral nerves. The evolution from the initial descriptions of neuropathies of presumed nutritional aetiology and later the recognition of two distinct subgroups, an ataxic neuropathy and a spastic myelopathy, are highlighted. The link between the natural history of human T-cell leukaemia/lymphoma virus type-1 (HTLV-1) infection and the immunopathogenesis of tropical spastic paraparesis is explored.

Este examen sigue las contribuciones de investigadores del Caribe encaminadas a mejorar la comprensión de los mecanismos de la enfermedad, rasgos clínicos y la etiología de los síndromes neurológicos que se manifiestan como enfermedades de la médula espinal y los nervios periféricos. El trabajo resalta la evolución de las descripciones iniciales de las neuropatías de etiología nutricional presuntiva y el posterior reconocimiento de dos subgrupos claramente distintos: la neuropatía atáxica, y la mielopatía espástica. Se explora el vínculo entre la historia natural de la infección por el virus humano de células tipo 1 (HTLV-1) en la leucemia/linfoma, y la inmunopatogénesis de la paraparesia espástica tropical.

Rinite crônica em portadores do HTLV-1: estudo histopatológico / Chronic rhinitis in HTLV-1 carriers: a histopathologic study

A histopatologia nasal de portadores do HTLV-1 com rinite crônica é desconhecida. OBJETIVO: Descrever aspectos histopatológicos de portadores do HTLV-1 com rinite crônica. CASUÍSTICA E MÉTODOS: Amostras de mucosa nasal de 10 portadores do HTLV-1 com rinite crônica, sendo oito com rinite alérgica e dois com rinite não alérgica, foram estudadas por microscopia de luz. Amostras de 10 pacientes com rinite alérgica não infectados pelo HTLV-1 serviram como controle. RESULTADOS: Fibrose subepitelial foi maior nos pacientes com rinite alérgica infectados pelo HTLV-1 (p=0,01), enquanto o espessamento da membrana basal foi maior nos controles (p=0,03). Houve tendência a menor eosinofilia e edema entre os infectados pelo HTLV-1, sem significância estatística (p=0,2). Para o infiltrado linfocítico, não houve diferença entre os pacientes com rinite alérgica infectados e não infectados (p=1,0). Fibrose subepitelial com infiltrado linfocítico de intensidade leve a moderada foram os achados encontrados nos dois portadores do HTLV-1 com rinite não alérgica. CONCLUSÕES: O estudo sugere que a infecção pelo HTLV-1 pode modificar a histopatologia da rinite alérgica, sobretudo por maior fibrose, e pode estar relacionada a uma rinite crônica não alérgica com infiltrado linfocítico.

The nasal histopathology of HTLV-1 carriers with chronic rhinitis is unknown. OBJECTIVE: To describe the histopathological features of HTLV-1 carriers with chronic rhinitis. MATERIALS AND METHODS: Biopsies of nasal mucosa of ten HTLV-1 carriers with chronic rhinitis (eight patients with allergic rhinitis and two patients with non-allergic rhinitis) were studied using a light microscope. Samples from ten patients with allergic rhinitis not infected with HTLV-1 were used as controls. RESULTS: Subepithelial fibrosis was more pronounced in patients with allergic rhinitis infected with HTLV-1 (p=0.01), while the basement membrane thickness was greater in controls (p=0.03). There was a trend towards less eosinophilia and edema among those infected with HTLV-1, without statistical significance (p=0.2). For the lymphocytic infiltrate, there was no difference between infected and not infected patients with allergic rhinitis (p=1.0). Subepithelial fibrosis associated to moderate or small number of lymphocytes were found in the two HTLV-1 carriers with non-allergic rhinitis. CONCLUSIONS: This study suggests HTLV-1 may modify the histopathology of allergic rhinitis, especially by promoting subepithelial fibrosis, and may be related to chronic non-allergic rhinitis with lymphocytic infiltrate.

HTLV 1 associated adult T cell lymphoma/leukemia a clinicopathologic, immunophenotypic tale of three cases from non-endemic region of south India.

Adult T cell lymphoma/leukemia is a peripheral T-cell neoplasm caused by human T-cell lymphotrophic virus-1, affects mostly adults with systemic involvement and poor prognosis. Diagnosis of adult T-Cell leukemia/Lymphoma is challenging. The clinico-pathologic and immuno-phenotypic features of the three cases will be presented.

Dermatitis infectiva: una revisión: a propósito de una experiencia peruana / Infective dermatitis: a review: about Peruvian experience

La dermatitis infectiva es una enfermedad eccematosa crónica de la niñez, que siempre compromete el cuero cabelludo y puede progresar a leucemia/linfoma de células T o a paraparesia espástica tropical. Es una condición dermatológica especial que está relacionada a la infección por el retrovirus linfotrópico humano a células T de tipo 1 (HTVL-1). En la niñez la forma de trasmisión más importante es a través de la lactancia materna. La expresión clínica así como su progresión están relacionadas con la carga viral, condiciones inmunológicas del paciente (infestación por Strongiloides stercoralis) y la intensidad de la respuesta inflamatoria. En esta revisión se destacan las características clínicas de esta entidad y se resaltan además sus hallazgos histopatológicos.

Infective dermatitis is a chronic, eczematous dermatitis of childhood that always involves the scalp and may progress to adult T-cell leukemia/lymphoma or tropical spastic paraparesis. It is a special dermatologic condition that has been linked to human T-cell lymphotropic virus type 1 (HTLV-1) infection. The most important route of transmission is vertical through breast-feeding. The clinical expression as well as its progression is related to viral load, immune status of patients (infestation by Strongyloides stercoralis) and the intensity of the inflammatory response. This review highlights the clinical features of this entity and also emphasizes its histopathological findings.

Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features / Coinfecção vírus da hepatite C-vírus linfotrópico de células T humanas: aspectos epidemiológicos, clínicos, laboratoriais e histopatológicos

Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2). The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.

Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2). A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e a gamaglutamiltranspeptidase foram mais altas no grupo VHC. Não houve diferença entre os grupos à análise histopatológica do fígado. Por análise discriminante definiram-se funções classificatórias, incluindo as variáveis sexo, faixa etária, uso de drogas endovenosas e parceiro sexual com hepatite, com acurácia discriminante alta para o grupo VHC.

Resonancia Magnética de médula espinal y cerebro en el correlato clínico de la paraparesia espástica progresiva que se asocia al virus humano linfotrópico tipo-I (HTLV-I) / Brain and spinal cord magnetic resonance imaging in spastic paraparesis associated to human T-lymphotropic virus

Background: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. Aim: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. Material and methods: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Results: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87 percent of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80 percent of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. Conclusions: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis.

Aconselhamento ao paciente infectado pelo vírus linfotrópico de cálulas-T humanas do tipo I e II (HTLV-I/II) / Advicing to human T-cell lymphotropic vírus type I and II (HTLV-I/II) infected persons

Indivíduos com resultados positivos para HTLV I/II devem receber informações sobre as vias de transmissão do vírus, doenças associadas, possibilidade de desenvolvimento de doenças e que estes vírus não provocam AIDS. Aconselha-se que o portador desta infecção seja instruído a compartilhar esta informação os profissionais de saúde aos quais procuram auxílio, não doar sangue, sêmen, órgãos ou tecidos, não compartilhar seringas ou similares, utilizar preservativos de látex e não amamentar, embora o risco de transmissão do HTL II por esta última via seja incerta. É recomendado que os indivíduos infectados realizem uma avaliação médica rotineira, incluindo exame físico, neurológico e avaliação hematológica. Os indivíduos que dsenvolverem alguma doença devem ser encaminhados a médicos especializados para receber tratamentos individualizados.

Multiple clinical manifestation of HTLV1 infection in a single patient

HTLV-1 infection is endemic in the Caribbean and several publications have reported the clinical disease entities seen in this population of patients. This case report is an account of a patient admitted to Kingstown General Hospital, St Vincent and the Grenadines, who had severe infective dermatitis, tropical spastic paraparesis (TSP) and Non-Hodgkin's Lymphoma (NHL). As far as we are aware, all three diseases have not been described in a single patient

Inflammatory myopathy on HTLV-I infection: case report

We describe a 41 years old woman who 17 years ago presented hypotonia and proximal muscular weakness in the upper and lower limbs. On neurological examination, the biceps, triceps and Achilles reflexes were absent; the brachioradialis reflexes were decreased and the patellar reflexes were normal. There was bilateral Babinski sign. The remainder of the neurological examination was unremarkable. In the investigation a myopathic pattern was found in the electromyography. The nerve-conduction study was normal; a ELISA method for HTLV-I antibodies was positive in the blood and in the cerebral spinal fluid. The muscle biopsy showed inflammatory myopathy, compatible with polymyositis. This paper focuses the polymyositis in the beginning of an HTLV-I infection case

Polimiosite associada a infecçao por HTLV-I: relato de caso / Polymyositis and HTLV-I infection: case report

Apresentamos o caso de mulher com 57 anos de idade apresentando polimiosite, associada a infecçao pelo HTLV-I, sem manifestaçoes clínicas de acomentimento do sistema nervoso central e periférico. Fazemos alguns comentários sobre os aspectos fisiopatológicos do envolvimento muscular nas infecçoes pelo HTLV-I

Paraparesia espástica tropical asociada a HTLV*I / Tropical spastic paraparesis asosciated HTLV-I infection

Reportamos el caso de un paciente con paraparesia espástica crónica, idiopática y no hereditaria en quien se encontró en los análisis de Western Blot la presencia de anticuerpos a Virus Linfotrópico T Humano de Tipo I (HTLV*I) en suero y en líquido cefaloraquídeo. Este es el primer caso de paraparesia espástica asociada a infección por HTLV*I detectado en nuestro Hospital y demuestra la urgente necesidad de realizar nuevos estudios para definir las características clínicas y epidemiológicas de esta enfermedad en nuestro país