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      Familial Transmission of Human T-cell Lymphotrophic Virus: Silent Dissemination of an Emerging but Neglected Infection

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          Abstract

          Background

          HTLV-1 is a retrovirus that causes lymphoproliferative disorders and inflammatory and degenerative diseases of the central nervous system in humans. The prevalence of this infection is high in parts of Brazil and there is a general lack of public health care programs. As a consequence, official data on the transmission routes of this virus are scarce.

          Objective

          To demonstrate familial aggregation of HTLV infections in the metropolitan region of Belém, Pará, Brazil.

          Method

          A cross-sectional study involving 85 HTLV carriers treated at an outpatient clinic and other family members. The subjects were tested by ELISA and molecular methods between February 2007 and December 2010.

          Results

          The prevalence of HTLV was 43.5% (37/85) for families and 25.6% (58/227) for the family members tested (95% CI: 1.33 to 3.79, P = 0.0033). Sexual and vertical transmission was likely in 38.3% (23/60) and 20.4% (29/142) of pairs, respectively (95% CI: 1.25 to 4.69, P = 0.0130). Positivity was 51.3% (20/39) and 14.3% (3/21) in wives and husbands, respectively (95% CI: 0.04 to 0.63, P = 0.0057). By age group, seropositivity was 8.0% (7/88) in subjects <30 years of age and 36.7% (51/139) in those of over 30 years (95% CI: 0.06 to 0.34, P<0.0001). Positivity was 24.1% (7/29) in the children of patients infected with HTLV-2, as against only 5.8% (4/69) of those infected with HTLV-1 (95% CI: 0.05 to 0.72, P = 0.0143).

          Conclusion

          The results of this study indicate the existence of familial aggregations of HTLV characterized by a higher prevalence of infection among wives and subjects older than 30 years. Horizontal transmission between spouses was more frequent than vertical transmission. The higher rate of infection in children of HTLV-2 carriers suggests an increase in the prevalence of this virus type in the metropolitan region of Belém.

          Author Summary

          Human T-cell lymphotropic virus (HTLV) has a slow replication rate and infection is characterized by low morbidity and mortality, as well as silent transmission within the population. While rare, HTLV-associated diseases are usually debilitating and life-threatening. The virus is endemic in the state of Pará (Brazil), although there have been no studies of the distribution of the virus within the local population. The results of the present study confirm the existence of familial aggregations of HTLV infection in the metropolitan region of the state capital, Belém. Considerably higher rates of sexual transmission of HTLV from men to women were also demonstrated. Rates of infection were similar for the two virus types, although HTLV-2 appears to be increasing in the population. The frequency of positivity among family members increased in direct proportion to age and was associated with a relatively large proportion of asymptomatic carriers. In addition, widespread ignorance of the virus increases the risk of transmission. The available evidence indicates that significant human suffering is caused by this virus in patients suffering complications, and this is little justification for the lack of intervention on the part of public health authorities, which might impede the ongoing proliferation of this infection in the population.

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          Most cited references34

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          HTLV-I associated myelopathy, a new clinical entity.

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            HTLV-I in the general population of Salvador, Brazil: a city with African ethnic and sociodemographic characteristics.

            The city of Salvador has the highest prevalence of HTLV-I among blood donors in Brazil. To study the prevalence of HTLV-I among the general population of Salvador, 30 "sentinel surveillance areas" were selected for the investigation of various infectious diseases, and 1385 individuals within these areas were surveyed according to a simple random sample procedure. ELISA was used to screen plasma samples for antibodies to HTLV-I, and the positive samples were tested by a confirmatory assay (Western blotting). The overall prevalence of HTLV-I was 1.76% (23/1385). Infection rates were 1.2% for males and 2.0% for females. Specific prevalence demonstrated an increasing linear trend with age. No one younger than 13 years of age was infected. Multivariate analysis estimated adjusted odds ratios for the association of HTLV-I with age of 9.7 (3.3; 30.4) for females and 12.3 (1.47; 103.1) for males. Less education and income might be associated with HTLV-I infection in females. Phylogenetic analysis of the long terminal repeat fragments showed that most of the samples belonged to the Latin American cluster of the Transcontinental subgroup (Cosmopolitan subtype). For the entire city of Salvador, it is estimated that approximately 40000 individuals are infected with HTLV-I. Our results suggest multiple post-Colombian introductions of African HTLV-Ia strains in Salvador.
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              Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2.

              HTLV-1 and HTLV-2 are highly related complex retroviruses that have been studied intensely for nearly three decades because of their association with neoplasia, neuropathology, and/or their capacity to transform primary human T lymphocytes. The study of HTLV also represents an attractive model that has allowed investigators to dissect the mechanism of various cellular processes, several of which may be critical steps in HTLV-mediated pathogenesis. Both HTLV-1 and HTLV-2 can efficiently immortalize and transform T lymphocytes in cell culture and persist in infected individuals or experimental animals. However, the clinical manifestations of these two viruses differ significantly. HTLV-1 is associated with adult T-cell leukemia (ATL) and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast, HTLV-2 is much less pathogenic with reports of only a few cases of variant hairy cell leukemia and neurological disease associated with infection. The limited number of individuals shown to harbor HTLV-2 in association with specific diseases has, to date, precluded convincing epidemiological demonstration of a definitive etiologic role of HTLV-2 in human disease. Therefore, it has become clear that comparative studies designed to elucidate the mechanisms by which HTLV-1 and HTLV-2 determine distinct outcomes are likely to provide fundamental insights into the initiation of multistep leukemogenesis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                June 2013
                13 June 2013
                : 7
                : 6
                : e2272
                Affiliations
                [1 ]Núcleo de Medicina Tropical, Universidade Federal do Pará, Belém, Pará, Brazil
                [2 ]Section of Virology, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil
                [3 ]Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil
                George Mason University, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CAdC RCMdS MSdS. Performed the experiments: CAdC KCYOF LdSCF DdSA AdCL RI ACRV JARdL LCM EAYI RCMdS MSdS. Analyzed the data: CAdC KCYOF LdSCF DdSA AdCL RI ACRV JARdL LCM EAYI RCMdS MSdS. Contributed reagents/materials/analysis tools: CAdC KCYOF LdSCF DdSA AdCL RI ACRV JARdL LCM EAYI RCMdS MSdS. Wrote the paper: CAdC KCYOF LdSCF DdSA AdCL RI ACRV JARdL LCM EAYI RCMdS MSdS.

                Article
                PNTD-D-12-01102
                10.1371/journal.pntd.0002272
                3681619
                23785534
                d43bf784-2cc9-4910-90b9-c0ad0bbaa592
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 August 2012
                : 29 April 2013
                Page count
                Pages: 7
                Funding
                The authors want to thank PPSUS/FAPESPA/CNPq (PROJ_428_9577372) and CAPES and PROPESP/UFPA and PADESP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Infectious Disease Control
                Neglected Tropical Diseases
                Sexually Transmitted Diseases
                Viral Diseases

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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