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      A Nationwide Antenatal Human T-Cell Leukemia Virus Type-1 Antibody Screening in Japan

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          Abstract

          Japan has been running a nationwide antenatal human T-cell leukemia virus type-1 (HTLV-1) antibody screening program since 2010 for the prevention of HTLV-1 mother-to-child transmission. As part of the program, pregnant women are invited to take an HTLV-1 antibody screening test, usually within the first 30 weeks of gestation, during regular pregnancy checkups. Pregnant women tested positive on the antibody screening test undergo a confirmatory test, either western blotting or line immunoassay. In indeterminate case, polymerase chain reaction (PCR) is used as a final test to diagnose infection. Pregnant women tested positive on a confirmatory or PCR test are identified as HTLV-1 carriers. As breastfeeding is a predominant route of postnatal HTLV-1 mother-to-child transmission, exclusive formula feeding is widely used as a postnatal preventive measure. Although there is insufficient evidence that short-term breastfeeding during ≤3 months does not increase the risk of mother-to-child transmission compared to exclusive formula feeding, this feeding method is considered if the mother is eager to breastfeed her child. However, it is important that mothers and family members fully understand that there is an increase in the risk of mother-to-child transmission when breastfeeding would be prolonged. As there are only a few clinical studies on the protective effect of frozen-thawed breastmilk feeding on mother-to-child transmission of HTLV-1, there is little evidence to recommend this feeding method. Further study on the protective effects of these feeding methods are needed. It is assumed that the risk of anxiety or depression may increase in the mothers who selected exclusive formula feeding or short-term breastfeeding. Thus, an adequate support and counseling for these mothers should be provided. In addition to raising public awareness of HTLV-1 infection, epidemiological data from the nationwide program needs to be collected and analyzed. In most cases, infected children are asymptomatic, and it is necessary to clarify how these children should be followed medically.

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          Most cited references78

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          Treatment and survival among 1594 patients with ATL.

          Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected.
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            Current prevalence of HTLV-1 in Japan as determined by screening of blood donors.

            Human T-cell leukemia virus type-1 (HTLV-1), a major source of adult T-cell leukemia and related diseases, is endemic to southwestern Japan. Mother-to-infant transmission via breast milk is an important route of infection, and establishing programs to prevent such transmission requires exact figures on the HTLV-1 prevalence rate and the number of carriers. Therefore, the seroprevalence of HTLV-1 among 1,196,321 Japanese first-time blood donors from 2006 to 2007 was investigated. A total of 3,787 of such donors were confirmed to be positive for anti-HTLV-1 antibody. By applying a fitness curve to the age ranges outside the blood donor age range, the present number of HTLV-1 carriers covering ages from 0 to 99 years was estimated to be at least 1.08 million in Japan; this value was 10% lower than that reported in 1988. The adjusted overall prevalence rates were estimated to be 0.66% and 1.02% in men and women, respectively. The peak in carrier numbers was found among individuals in their 70s, which is a shift from the previous peak observed in the 1988 database among individuals in their 50s. Carriers were distributed not only in the endemic southwestern region of Japan, but throughout the country, particularly in the greater Tokyo metropolitan area. By applying population projections, it was calculated that the carrier number will decrease by half in the next two decades; however, the carrier population will age over that interval, meaning that the age of patients with adult T-cell leukemia will also be higher. Copyright © 2011 Wiley Periodicals, Inc.
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              Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I.

              Adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, has been etiologically linked to the human retrovirus HTLV-I. Although a long latent period is suggested from migrant studies, little prospective information on the risk of developing ATL among persons with HTLV-I infection is available. We present here a model for ATL risk based upon age- and sex-specific HTLV-I seroprevalence data from a cross-sectional survey of 13,000 Jamaicans and ATL incidence data from a 2 1/2-year case-control study. By examining the age-specific incidence of ATL relative to both adult and childhood-acquired seropositivity versus childhood-acquired seropositivity alone, we provide evidence in support of the hypothesis that childhood infection with HTLV-I is important to the development of ATL. Using this model, the cumulative lifetime risk of ATL for those infected before age 20 is estimated to be 4.0% for males and 4.2% for females. Under this hypothesis, HTLV-I-associated diseases with shorter latent periods, such as tropical spastic paraparesis, should have a higher incidence in adult females than in adult males.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                09 April 2020
                2020
                : 11
                : 595
                Affiliations
                [1] 1Showa University Hospital , Tokyo, Japan
                [2] 2Department of Pediatrics, Showa University School of Medicine , Tokyo, Japan
                [3] 3Japan Association of Obstetricians and Gynecologists , Tokyo, Japan
                [4] 4Japanese Pediatric Association , Tokyo, Japan
                [5] 5The University of Toyama , Toyama, Japan
                [6] 6Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences , Nagasaki, Japan
                [7] 7Faculty of Medicine, School of Health Sciences, Kagoshima University , Kagoshima, Japan
                [8] 8Graduate School of Frontier Sciences, The University of Tokyo , Tokyo, Japan
                [9] 9Future Center Initiative, and Research Hospital of the Institute of Medical Science, The University of Tokyo , Tokyo, Japan
                Author notes

                Edited by: Akio Adachi, Kansai Medical University, Japan

                Reviewed by: Antoine Gessain, Institut Pasteur, France; Edward Murphy, University of California, San Francisco, United States

                *Correspondence: Kazuo Itabashi, kitaba@ 123456med.showa-u.ac.jp

                This article was submitted to Virology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.00595
                7160230
                32328047
                6fea0fe6-5611-4353-9434-dc67a6417520
                Copyright © 2020 Itabashi, Miyazawa, Sekizawa, Tokita, Saito, Moriuchi, Nerome, Uchimaru and Watanabe.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 December 2019
                : 18 March 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 89, Pages: 12, Words: 0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                human t-cell leukemia virus type-1,nationwide antenatal screening,confirmatory test,mother-to-child transmission,infection,prevention

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