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      Brazilian Protocol for Sexually Transmitted Infections 2020: human T-cell lymphotropic virus (HTLV) infection

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          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.

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          HTLV-1/2 transmission can occur through blood transfusion and derivatives, injectable drug use, organ transplantation, unprotected sexual intercourse, and vertical transmission.

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          Most cited references233

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          Epidemiological Aspects and World Distribution of HTLV-1 Infection

          The human T-cell leukemia virus type 1 (HTLV-1), identified as the first human oncogenic retrovirus 30 years ago, is not an ubiquitous virus. HTLV-1 is present throughout the world, with clusters of high endemicity located often nearby areas where the virus is nearly absent. The main HTLV-1 highly endemic regions are the Southwestern part of Japan, sub-Saharan Africa and South America, the Caribbean area, and foci in Middle East and Australo-Melanesia. The origin of this puzzling geographical or rather ethnic repartition is probably linked to a founder effect in some groups with the persistence of a high viral transmission rate. Despite different socio-economic and cultural environments, the HTLV-1 prevalence increases gradually with age, especially among women in all highly endemic areas. The three modes of HTLV-1 transmission are mother to child, sexual transmission, and transmission with contaminated blood products. Twenty years ago, de Thé and Bomford estimated the total number of HTLV-1 carriers to be 10–20 millions people. At that time, large regions had not been investigated, few population-based studies were available and the assays used for HTLV-1 serology were not enough specific. Despite the fact that there is still a lot of data lacking in large areas of the world and that most of the HTLV-1 studies concern only blood donors, pregnant women, or different selected patients or high-risk groups, we shall try based on the most recent data, to revisit the world distribution and the estimates of the number of HTLV-1 infected persons. Our best estimates range from 5–10 millions HTLV-1 infected individuals. However, these results were based on only approximately 1.5 billion of individuals originating from known HTLV-1 endemic areas with reliable available epidemiological data. Correct estimates in other highly populated regions, such as China, India, the Maghreb, and East Africa, is currently not possible, thus, the current number of HTLV-1 carriers is very probably much higher.
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            Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87).

            The following diagnostic criteria are proposed to classify four clinical subtypes of HTLV-1 associated adult T-cell leukaemia-lymphoma (ATL): (1) Smouldering type, 5% or more abnormal lymphocytes of T-cell nature in PB, normal lymphocyte level (less than 4 x 10(9)/l), no hypercalcaemia (corrected calcium level less than 2.74 mmol/l), lactate dehydrogenase (LDH) value of up to 1.5 x the normal upper limit, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone and gastrointestinal tract, and neither ascites nor pleural effusion. Skin and pulmonary lesion(s) may be present. In case of less than 5% abnormal T-lymphocytes in PB, at least one of histologically-proven skin and pulmonary lesions should be present. (2) Chronic type, absolute lymphocytosis (4 x 10(9)/l or more) with T-lymphocytosis more than 3.5 x 10(9)/l, LDH value up to twice the normal upper limit, no hypercalcaemia, no involvement of CNS, bone and gastrointestinal tract, and neither ascites nor pleural effusion. Lymphadenopathy and involvement of liver, spleen, skin, and lung may be present, and 5% or more abnormal T-lymphocytes are seen in PB in most cases . (3) Lymphoma type, no lymphocytosis, 1% or less abnormal T-lymphocytes, and histologically-proven lymphadenopathy with or without extranodal lesions. (4) Acute type, remaining ATL patients who have usually leukaemic manifestation and tumour lesions, but are not classified as any of the three other types. A total of 818 ATL patients with a mean age of 57 years, newly diagnosed from 1983 to 1987, were analysed by this criteria. There were 448 males and 370 females, and 253 were still alive with a median follow-up time of 13.3 months from diagnosis, while 565 were dead with a median survival time (MST) of 5.4 months. MST was 6.2 months for acute type, 10.2 months for lymphoma type, 24.3 months for chronic type, and not yet reached for smouldering type. Projected 2- and 4-year survival rates were 16.7% and 5.0% for acute type, 21.3% and 5.7% for lymphoma type, 52.4% and 26.9% for chronic type, 77.7% and 62.8% for smouldering type, respectively. Distinct clinical features and laboratory findings of each clinical subtype are described.
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              Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting.

              Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with a retrovirus designated human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories: acute, lymphoma, chronic, and smoldering types. The chronic and smoldering subtypes are considered indolent and are usually managed with watchful waiting until disease progression, analogous to the management of some patients with chronic lymphoid leukemia (CLL) or other indolent histology lymphomas. Patients with aggressive ATL generally have a poor prognosis because of multidrug resistance of malignant cells, a large tumor burden with multiorgan failure, hypercalcemia, and/or frequent infectious complications as a result of a profound T-cell immunodeficiency. Under the sponsorship of the 13th International Conference on Human Retrovirology: HTLV, a group of ATL researchers joined to form a consensus statement based on established data to define prognostic factors, clinical subclassifications, and treatment strategies. A set of response criteria specific for ATL reflecting a combination of those for lymphoma and CLL was proposed. Clinical subclassification is useful but is limited because of the diverse prognosis among each subtype. Molecular abnormalities within the host genome, such as tumor suppressor genes, may account for these diversities. A treatment strategy based on the clinical subclassification and prognostic factors is suggested, including watchful waiting approach, chemotherapy, antiviral therapy, allogeneic hematopoietic stem-cell transplantation (alloHSCT), and targeted therapies.
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                Author and article information

                Journal
                Rev Soc Bras Med Trop
                Rev Soc Bras Med Trop
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Sociedade Brasileira de Medicina Tropical - SBMT
                0037-8682
                1678-9849
                17 May 2021
                2021
                : 54
                : Suppl 1
                : e2020605
                Affiliations
                [1 ]Imperial College London, Department of Infectious Disease, London, United Kingdom.
                [2 ] Universidade Federal da Bahia, Faculdade de Medicina, Salvador, BA, Brasil.
                [3 ] Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil.
                [4 ] Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil.
                [5 ] Universidade Federal do Pará, Instituto de Ciências Biológicas, Belém, PA, Brasil.
                Author notes
                Corresponding author: Ricardo Ishak. e-mail: rishak@ 123456ufpa.br

                Authors' contributions: Rosadas C, Brites C, Arakaki-Sanchez D, Casseb J, and Ishak R contributed with the concept, design, drafting, and critical reviewing of the manuscript. All authors approved the final version, and they are responsible for all aspects of the work, including the assurance of its accuracy, precision, and integrity.

                Author information
                http://orcid.org/0000-0002-3922-5667
                http://orcid.org/0000-0002-4673-6991
                http://orcid.org/0000-0001-8026-2876
                http://orcid.org/0000-0002-4553-2559
                http://orcid.org/0000-0002-4741-6201
                Article
                01208
                10.1590/0037-8682-605-2020
                8210483
                34008723
                a45ffdf4-f1ce-49df-90ff-d30a1b7d77f9

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 01 February 2021
                : 10 March 2021
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 209
                Categories
                Consensus

                human t-cell lymphotropic virus 1,sexually transmitted diseases,diagnosis,signs and symptoms,disease prevention

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