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      Molecular detection of human T-lymphotropic virus type 1 infection among oncology patients in Germany: A retrospective view

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          Abstract

          Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL). Public Health authorities in many countries have implemented routine blood-donor tests for HTLV-specific antibodies; but this is not the case for Germany since the reported prevalence is very low (7/100,000). With the aim to evaluate retrospectively the presence of HTLV-1 among oncology patients in this country, samples stored at the Universitätsklinikum Freiburg, were analyzed. For this purpose, two different nested-PCR (n-PCR) protocols have been modified and set up for HTLV-1 detection. One positive case was detected by n-PCR among 406 samples (0,25%) in a period of 5 years (2008–2012) corresponding to a T-Cell Lymphoma. Despite the low prevalence, this virus is circulating in Germany, probably due to the increasing numbers of immigrants in these last years. Physicians should consider HTLV-1 infection and suspect it taking in account the ethnic and relation to endemic regions regardless the patient's residence.

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          Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians

          Background The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). Methodology/Principal findings 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Conclusion/Significance Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.
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            Differential diagnosis of HTLV-I and HTLV-II infections by restriction enzyme analysis of 'nested' PCR products.

            A 'nested' polymerase chain reaction (PCR) assay is described which is capable of detecting single copies of human T-cell lymphotropic virus (HTLV) in genomic DNA extracted from peripheral blood mononuclear cells (PBMCs). A single set of 'nested' oligonucleotide primers, based on the highly conserved tax/rex region of the viral genome, was able to detect both HTLV-I and HTLV-II proviral sequences in clinical samples of diverse geographical origins, from the United States, Great Britain, Japan, the Caribbean, Italy, Greece, Iraq and West Africa. Rapid discrimination between HTLV-I and HTLV-II infections was achieved by restriction enzyme analysis of unpurified second-round PCR products, even in those cases in which serological assays had failed to provide a definitive result. Over a 2-year period, a total of 53 HTLV infections (37 HTLV-I and 16 HTLV-II) were identified by this technique and complete concordance with serological typing, available in 41 cases, was observed.
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              HTLV-I/II prevalence in different geographic locations.

              Human T-cell lymphotropic virus (HTLV) type I (HTLV-I) is the etiological agent of adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-II is a closely related virus, and this infection is not clearly associated with clinical disease, although neurologic disorders are observed resembling HAM/TSP. Prevalence rates for HTLV-I infection in the general population are greater than 1% in the Caribbean Basin, Central Africa, and South Japan. In most other areas in the world, as far as we know, HTLV-I/II infections are mainly found in high-risk groups (ie, immigrants from endemic areas, their offspring, their sexual contacts and in patients and intravenous injection users attending sexually transmitted disease clinics). Also, a high rate of infection for both HTLV-I and HTLV-II infection was observed in the native Amerindian population in North America as well as South America. Blood donors are routinely screened for HTLV-I/II in North America, several countries in Europe, Japan, and Taiwan.
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                Author and article information

                Contributors
                Role: Data curationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Validation
                Role: Validation
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 May 2019
                2019
                : 14
                : 5
                : e0217560
                Affiliations
                [1 ] Institut für Klinische Pathologie, Universitätsklinikum Freiburg, Freiburg, Germany
                [2 ] Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
                [3 ] UW School of Medicine and Public Health, Madison, Wisconsin, United States of America
                Institute of Tropical Medicine Antwerp, BELGIUM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-5959-9092
                Article
                PONE-D-19-05203
                10.1371/journal.pone.0217560
                6538170
                31136642
                27be8ef6-cce6-45a2-b9ff-cebf93897385
                © 2019 Ruggieri et al

                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
                : 21 February 2019
                : 14 May 2019
                Page count
                Figures: 5, Tables: 1, Pages: 9
                Funding
                Funded by: MINCYT-BMBF
                Award ID: AL/14/08-01DN15025
                Funded by: CONICET
                Award ID: PICT 20161033
                Award Recipient :
                The authors are grateful for the funding support by the International Cooperation Project MINCYT-BMBF 2014 (Bilateral project Argentina-Germany AL/14/08-01DN15025) (MB and PF); National Scientific and Technical Research Council (CONICET: PICT 20161033) (MB) and German Academic Exchange Service (DAAD) for the scholarship (MR). The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing. The funders had no role in the study design, the collection, analysis and interpretation of the data, nor in the decision to publish, or preparation of the manuscript.
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