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      Human T lymphotropic virus types 1 and 2: a point of view

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          Abstract

          Reported at the beginning of the 1980s, Human T lymphotropic viruses type 1 and 2 (HTLV1, HTLV 2) were the first retroviruses to have been detected in human beings. HTLV 1 was isolated from adult T-cell leukemia (ATL) and first described by Takatsuki et al. in Japan in 1976, as a malignancy that only affects T cells and only in adults(1, 2). Albeit infrequent, HTLV-1 infection may lead to severe morbidity when it causes malignancy or degenerative conditions. The virus can also cause mild immune deficiency even in the absence of any malignancy. Fatal neurologic diseases, such as HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), uveitis, iritis, peripheral neuropathies, and arthritis can also be caused by HTLV-1. All these diseases can be autoimmune, but their exact mechanisms are not yet known(3). Human T lymphotropic virus type 2 (HTLV-2) was discovered in a patient with a T-cell variant of hairy cell leukemia. The virus has been associated with increased mortality and morbidity, risk for pneumonia and bronchitis, urinary tract infections, and rare neurologic manifestations. HTLV infection is life-long and disease symptoms can manifest some 20-40 years post-infection(4-6). Recently, an increased prevalence of psychiatric symptoms was described among HTLV-seropositive patients(7,8). Prevalence greatly varies in different regions of the world. HTLV-1 is endemic in southwestern Japan, in the Caribbean Islands, and in Central Africa. Carriers have been identified in South America, Papua New Guinea, the Solomon Islands, South China, and other isolated populations such as the Australia Aborigines. HTLV-2 can also be found in some Native American populations. HTLV-1 is transmitted by blood, through sexual contact, injectable drug use and from mother to offspring through breastfeeding(1-6). HTLV-2 is most often found in injectable drug users and in their sexual partners. As a consequence of the transmission routes, all blood donated at the Red Cross Blood Centers in Japan has been subjected to HTLV-1 antibody screening since November 1986 and carrier mothers have been instructed to refrain from breastfeeding to prevent HTLV-1 transmission(9-11). In the United States, screening began at the end of 1988 and in the entire world since 1990(12-15). At the beginning, blood donor screening was performed with enzyme immunoassays (EIAs) for antibodies against HTLV-1 and later against HTLV-1/2, which led to the unnecessary deferral of a great number of individuals. Confirmatory testing could be performed by Western blot but this was expensive and took a long time. Nowadays screening is performed by chemiluminescent immunoassay with a lower risk of false positives(16). Up to now there is no available licensed confirmatory test. The efficacy of this test reduces the number of indeterminate results and could be better than the lookback procedure for HTLV-1/2(17). Confirmatory testing by polymerase chain reaction (PCR), albeit expensive, is used in the great majority of blood banks around the world. The same serological difficulties are observed in Brazil as confirmatory testing is only performed by research groups in some blood banks. HTLV-1/2 infection is endemic in Brazil(18-22) and testing blood donors has been mandatory since 1993. Recently, Carneiro-Proentti et al.(22) analyzed all blood donations of three regional Brazilian Blood Banks located in São Paulo, Minas Gerais and Pernambuco during 2007-2009. Serological results were confirmed by Western blot. Results concerning donor age, gender, education status, and race confirmed the previously published results from other Brazilian blood banks(23,25). Prevalence increased with age, was higher among women and Blacks and was inversely correlated to the level of education. Prevalence variations in different blood banks were expected and probably reflect population origins (higher in Pernambuco than in Sao Paulo and Minas Gerais). The overall incidence rate was 3.59 per 100,000 person-years and the residual risk was 5.0/100,000 per repeat donor blood unit transfused, that is, lower than previously reported in southern Brazil(25). Seroprevalence rates were in the order of 1 to 2 per thousand first time donors which is higher than in the United States and Europe but lower than in the Brazilian general population(24). Besides HTLV screening difficulties, the public health system is also not prepared to confirm and counsel serum-positive donors thus creating a difficult situation as the virus can be transmitted through breastfeeding and the disease can appear almost 30 years after a serological positive result. Preventive measures, the follow up of donors and confirmatory testing procedures must be improved. In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Lima et al. bring new data from the Caruaru Blood Center in Pernambuco(26).

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          High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey.

          Mashhad, in the northeast of Iran has been suggested as an endemic area for human T cell lymphotropic virus type I (HTLV-I) infection since 1996. We performed a community-based seroepidemiology study to examine the prevalence and risk factors for HTLV-I infection in the city of Mashhad. Between May and September 2009, overall 1678 subjects from all the 12 geographical area of Mashhad were selected randomly by multistage cluster sampling for HTLV antibody. The study population included 763 males and 915 females, with the mean age of 29.1 ± 18.5 years. 1654 serum samples were assessed for HTLV antibody using ELISA and reactive samples were confirmed by Western blot and PCR. The overall prevalence of HTLV-I infection in whole population was 2.12% (95% CI, 1.48-2.93) with no significant difference between males and females (p = 0.093) and the prevalence of HTLV-II seropositivity was 0.12% (95% CI, 0.02-0.44). The HTLV-I Infection was associated with age (p<0.001), marital status (p<0.001), education (p = 0.047), and history of blood transfusion (p = 0.009), surgery (p<0.001), traditional cupping (p = 0.002), and hospitalization (p = 0.004). In logistic regression analysis, age was the only variable that had a significant relation with the infection (p = 0.006, OR = 4.33). Our results demonstrated that Mashhad still remains an endemic area for HTLV-I infection despite routine blood screening. Thus, further strategies are needed for prevention of the virus transmission in whole population. Copyright © 2011 Elsevier B.V. All rights reserved.
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            The discovery of the first human retrovirus: HTLV-1 and HTLV-2

            I describe here the history leading up to and including my laboratory's discovery of the first human retrovirus, HTLV-I, and its close relative, HTLV-II. My efforts were inspired by early work showing a retroviral etiology for leukemias in various animals, including non-human primates. My two main approaches were to develop criteria for and methods for detection of viral reverse transcriptase and to identify growth factors that could support the growth of hematopoietic cells. These efforts finally yielded success following the discovery of IL-2 and its use to culture adult T cell lymphoma/leukemia cells.
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              Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki

              In late 2010, the nation-wide screening of pregnant women for human T-lymphotropic virus type 1 (HTLV-1) infection was implemented in Japan to prevent milk-borne transmission of HTLV-1. In the late 1970s, recognition of the adult T-cell leukemia (ATL) cluster in Kyushu, Japan, led to the discovery of the first human retrovirus, HTLV-1. In 1980, we started to investigate mother-to-child transmission (MTCT) for explaining the peculiar endemicity of HTLV-1. Retrospective and prospective epidemiological data revealed the MTCT rate at ∼20%. Cell-mediated transmission of HTLV-1 without prenatal infection suggested a possibility of milk-borne transmission. Common marmosets were successfully infected by oral inoculation of HTLV-1 harboring cells. A prefecture-wide intervention study to refrain from breast-feeding by carrier mothers, the ATL Prevention Program Nagasaki, was commenced in July 1987. It revealed a marked reduction of HTLV-1 MTCT by complete bottle-feeding from 20.3% to 2.5%, and a significantly higher risk of short-term breast-feeding (<6 months) than bottle-feeding (7.4% vs. 2.5%, P < 0.001).
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                Author and article information

                Journal
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Revista Brasileira de Hematologia e Hemoterapia
                Associação Brasileira de Hematologia e Hemoterapia
                1516-8484
                1806-0870
                2013
                : 35
                : 4
                : 240-241
                Affiliations
                Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil
                Author notes
                Corresponding author: Angela Cristina Malheiros Luzo, Centro de Hematologia e Hemoterapia de Campinas, Universidade Estadual de Campinas- Unicamp, Rua Carlos Chagas, 450 - Cidade Universitária "Prof. Zeferino Vaz", 13083-878 Distrito de Barão Geraldo - Campinas, SP - Brazil, luzo@ 123456unicamp.br
                Article
                10.5581/1516-8484.20130096
                3789426
                4a8a6b88-65d5-4b67-977b-b1f888ac3419

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 July 2013
                : 24 July 2013
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                Scientific Comments

                Hematology
                Hematology

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