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      Prevalence of HTLV-1/2 in Pregnant Women Living in the Metropolitan Area of Rio de Janeiro

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          Abstract

          Background

          HTLV-1/2 infection can cause severe and disabling diseases in children and adults. The aim of the study was to estimate the prevalence of HTLV-1/2 infection in pregnant women living in the metropolitan area of Rio de Janeiro.

          Methodology/Principal Findings

          1,204 pregnant women were tested upon hospital admission for delivery in two public hospitals in the cities of Rio de Janeiro and Mesquita, between November, 2012 and April, 2013. The samples were screened by chemiluminescent microparticle immunoassay (CMIA) and reactive ones were confirmed by Western blot (WB). Epi-info software was used for building the database and performing the statistical analysis. Eight patients had confirmed HTLV-1/2 infection (7 HTLV-1, one HTLV-2), equivalent to a prevalence rate of 0.66%. Two further reactive screening tests had negative Western blot results and therefore were considered negative in the statistical analysis. All HTLV-1/2-positive patients were born in Rio de Janeiro, most were non-Caucasian (87.5%), in a stable relationship (62.5%), had at least ten years of formal education (62.5%) and a monthly family income of up to US$600.00 (87.5%). There was only one case of coinfection with syphilis and none with HIV. The mean age of the infected women was 28.4 (SD = 6.3) years and of the seronegative ones was 24.8 (SD = 6.5) (p = 0.10). The median number of pregnancies were 3.0 and 1.0 (p = 0.06) and the median number of sexual partners were 3.5 and 3.0 (p = 0.33) in the seropositive and negative groups, respectively. There were no statistically significant differences between the groups.

          Conclusions/Significance

          A significant prevalence of HTLV-1/2 was found in our population. The socio-epidemiological profile of carrier mothers was similar to the controls. Such findings expose the need for a public health policy of routine HTLV-1/2 screening in antenatal care, since counselling and preventive measures are the only strategies currently available to interrupt the chain of transmission and the future development of HTLV-1/2-related diseases.

          Author Summary

          HTLV-1/2 are retroviruses transmitted by blood products, sexual contact and from mother to child, mainly through breastfeeding. The infection has a characteristic geographical distribution with endemic areas often neighbouring very low prevalence areas. Infection is life long and although asymptomatic in most cases, it can cause severe and disabling diseases in children and adults. There is currently no cure, vaccine or effective treatment for HTLV-1/2 infections. Our research is the first to study the prevalence of HTLV-1/2 in pregnant women living in the metropolitan area of Rio de Janeiro, the second largest in Brazil. 1,204 pregnant women were tested upon hospital admission for delivery in two public hospitals in the cities of Rio de Janeiro and Mesquita, between November, 2012 and April, 2013 and a significant prevalence of HTLV-1/2 was found (0.66%). The socio-epidemiological profile of carrier mothers was similar to the controls'. Epidemiological knowledge is fundamental for the elaboration of public health policies such as routine HTLV-1/2 screening in antenatal care, since counselling and preventive measures, mainly avoidance of breastfeeding, are the only strategies currently available to interrupt the chain of transmission and the future development of HTLV-1/2-related diseases.

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          Most cited references28

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          Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.

          Retrovirus particles with type C morphology were found in two T-cell lymphoblastoid cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes obtained from a patient with a cutaneous T-cell lymphoma (mycosis fungoides). The cell lines continuously produce these viruses, which are collectively referred to as HTLV, strain CR(HTLV(CR)). Originally, the production of virus from HUT 102 cells required induction with 5-iodo-2'-deoxyuridine, but the cell line became a constitutive producer of virus at its 56th passage. Cell line CTCL-3 has been a constitutive producer of virus from its second passage in culture. Both mature and immature extracellular virus particles were seen in thin-section electron micrographs of fixed, pelleted cellular material; on occasion, typical type C budding virus particles were seen. No form of intracellular virus particle has been seen. Mature particles were 100-110 nm in diameter, consisted of an electron-dense core surrounded by an outer membrane separated by an electron-lucent region, banded at a density of 1.16 g/ml on a continuous 25-65% sucrose gradient, and contained 70S RNA and a DNA polymerase activity typical of viral reverse transcriptase (RT; RNA-dependent DNA nucleotidyltransferase). Under certain conditions of assay, HTLV(CR) RT showed cation preference for Mg(2+) over Mn(2+), distinct from the characteristics of cellular DNA polymerases purified from human lymphocytes and the RT from most type C viruses. Antibodies to cellular DNA polymerase gamma and anti-bodies against RT purified from several animal retroviruses failed to detectably interact with HTLV(CR) RT under conditions that were positive for the respective homologous DNA polymerase, demonstrating a lack of close relationship of HTLV(CR) RT to cellular DNA polymerases gamma or RT of these viruses. Six major proteins, with sizes of approximately 10,000, 13,000, 19,000, 24,000, 42,000, and 52,000 daltons, were apparent when doubly banded, disrupted HTLV(CR) particles were chromatographed on a NaDodSO(4)/polyacrylamide gel. The number of these particle-associated proteins is consistent with the expected proteins of a retrovirus, but the sizes of some are distinct from those of most known retroviruses of the primate subgroups.
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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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              Pathways of cell-cell transmission of HTLV-1

              The deltaretroviruses human T cell lymphotropic virus type 1 (HTLV-1) and human T cell lymphotropic virus type 2 (HTLV-2) have long been believed to differ from retroviruses in other genera by their mode of transmission. While other retroviruses were thought to primarily spread by producing cell-free particles that diffuse through extracellular fluids prior to binding to and infecting target cells, HTLV-1 and HTLV-2 were believed to transmit the virus solely by cell–cell interactions. This difference in transmission was believed to reflect the fact that, relative to other retroviruses, the cell-free virions produced by HTLV-infected cells are very poorly infectious. Since HTLV-1 and HTLV-2 are primarily found in T cells in the peripheral blood, spread of these viruses was believed to occur between infected and uninfected, T cells, although little was known about the cellular and viral proteins involved in this interaction. Recent studies have revealed that the method of transmission of HTLV is not unique: other retroviruses including human immunodeficiency virus (HIV) are also transmitted from cell-to-cell, and this method is dramatically more efficient than cell-free transmission. Moreover, cell–cell transmission of HTLV-1, as well as HIV, can occur following interactions between dendritic cells and T cells, as well as between T cells. Conversely, other studies have shown that cell-free HTLV-1 is not as poorly infectious as previously thought, since it is capable of infecting certain cell types. Here we summarize the recent insights about the mechanisms of cell–cell transmission of HTLV-1 and other retroviruses. We also review in vitro and in vivo studies of infection and discuss how these finding may relate to the spread of HTLV-1 between individuals.
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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
                September 2014
                4 September 2014
                : 8
                : 9
                : e3146
                Affiliations
                [1 ]Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil
                [2 ]Centro Universitário Serra dos Órgãos (UNIFESO), Teresópolis, Rio de Janeiro, Brazil
                [3 ]Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brazil
                [4 ]Hospital Estadual da Mãe – Mesquita, Rio de Janeiro, Brazil
                [5 ]Universidade do Grande Rio (UNIGRANRIO), Duque de Caxias, Rio de Janeiro, Brazil
                University of Washington, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DLMM SRT AJBT MNB. Performed the experiments: DLMM SRT AJBT MNB DBSB SAMT. Analyzed the data: DLMM NCPR. Contributed reagents/materials/analysis tools: AJBT LHCV MNB. Contributed to the writing of the manuscript: DLMM DBSB SRT AJBT MNB SAMT NCPR. Review: DLMM DBSB.

                Article
                PNTD-D-14-00517
                10.1371/journal.pntd.0003146
                4154655
                25188386
                bdabf087-eaaf-42dc-bde2-80f481c5331d
                Copyright @ 2014

                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
                : 28 March 2014
                : 30 June 2014
                Page count
                Pages: 5
                Funding
                This study was supported by a grant from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ - E-26/110.351/2012) to SRT and DLMM ( www.faperj.br). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Tropical Diseases
                Women's Health
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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