{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:24:19Z","timestamp":1787891059013,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,26]],"date-time":"2019-12-26T00:00:00Z","timestamp":1577318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Despite its relatively low incidence of associated diseases, Human T-cell Leukemia Virus-1 (HTLV-1) infection was reported to carry a significant risk of mortality in several endemic areas. HTLV-1-associated diseases, adult T-cell leukemia\/lymphoma (ATLL) and HTLV-1-associated myelopathy\/tropical spastic paraperesis (HAM\/TSP), as well as frequent coinfections with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Strongyloides stercoralis were associated to increased morbidity and mortality of HTLV-1 infection. Objective: To determine the mortality rate and its associated variables from an open cohort started in July 1997 at the HTLV Clinic, Emilio Ribas Institute (IIER), a major infectious disease hospital in S\u00e3o Paulo, Brazil. Methods: Since inception up to September 2018, we admitted 727 HTLV-1-infected individuals, with a rate of 30\u201350 new admissions per year. All patient data, including clinical and laboratory data, were regularly updated throughout the 21-year period, using a dedicated REDCap database. The Ethical Board of IIER approved the protocol. Results: During 21 years of clinical care to people living with HTLV-1 in the S\u00e3o Paulo region, we recruited 479 asymptomatic HTLV-1-infected individuals and 248 HAM\/TSP patients, of which 632 remained under active follow-up. During a total of 3800 person-years of follow-up (maximum follow-up 21.5 years, mean follow-up 6.0 years), 27 individuals died (median age of 51.5 years), of which 12 were asymptomatic, one ATLL patient and 14 HAM\/TSP patients. HAM\/TSP diagnosis (but neither age nor gender) was a significant predictor of increased mortality by univariate and multivariate (hazard ratio (HR) 5.03, 95% CI [1.96\u201312.91], p = 0.001) Cox regression models. Coinfection with HIV\/HCV was an independent predictor of increased mortality (HR 15.08; 95% CI [5.50\u201341.32]; p &lt; 0.001), with AIDS-related infections as a more frequent cause of death in asymptomatics (6\/13; p = 0.033). HIV\/HCV-negative fatal HAM\/TSP cases were all female, with urinary tract infection and decubitus ulcer-associated sepsis as the main cause of death (8\/14, p = 0.002). Conclusions: All-cause mortality among people living with HTLV-1 in S\u00e3o Paulo differs between asymptomatic (2.9%) and HAM\/TSP patients (7.3%), independent of age and gender. We observe a dichotomy in fatal cases, with HAM\/TSP and HIV\/HCV coinfection as independent risk factors for death. Our findings reveal an urgent need for public health actions, as the major causes of death, infections secondary to decubitus ulcers, and immune deficiency syndrome (AIDS)-related infections, can be targeted by preventive measures.<\/jats:p>","DOI":"10.3390\/pathogens9010025","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T05:37:08Z","timestamp":1577425028000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in S\u00e3o Paulo, Brazil"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-0263","authenticated-orcid":false,"given":"Rosa Maria N.","family":"Marcusso","sequence":"first","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Van Weyenbergh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Victor Luisi","family":"de Moura","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via Esper","family":"Dahy","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-2575","authenticated-orcid":false,"given":"Aline","family":"de Moura Brasil Matos","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-1992","authenticated-orcid":false,"given":"Michel E. J.","family":"Haziot","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"},{"name":"Institute of Tropical Medicine of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Augusto M.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerusa","family":"Smid","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane","family":"Assone","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"},{"name":"Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, Medical School, University of S\u00e3o Paulo Brazil, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4553-2559","authenticated-orcid":false,"given":"Jorge","family":"Casseb","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"},{"name":"Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, Medical School, University of S\u00e3o Paulo Brazil, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4084-7973","authenticated-orcid":false,"given":"Augusto C\u00e9sar Penalva","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases \u201cEmilio Ribas\u201d (IIER) of S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/S1473-3099(07)70081-6","article-title":"Human T-lymphotropic virus 1: Recent knowledge about an ancient infection","volume":"7","author":"Verdonck","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","article-title":"Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis","volume":"326","author":"Gessain","year":"1985","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological aspects and world distribution of HTLV-1 infection","volume":"3","author":"Gessain","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/infdis\/162.2.347","article-title":"Patterns of HIV-1 and HTLV-I\/II in intravenous drug abusers from the middle atlantic and central regions of the USA","volume":"162","author":"Lee","year":"1990","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF01730366","article-title":"HTLV-I and HTLV-II infections among HIV-1 seropositive patients in Sao Paulo, Brazil","volume":"10","author":"Casseb","year":"1994","journal-title":"Eur. J. Epidemiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1089\/aid.1997.13.1639","article-title":"Testing problems in diagnosing HTLV infection among intravenous drug users with AIDS in Sao Paulo City, Brazil","volume":"13","author":"Casseb","year":"1997","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7742","DOI":"10.1038\/s41598-018-25939-y","article-title":"Risk factors associated with HTLV-1 vertical transmission in Brazil: Longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring","volume":"8","author":"Paiva","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"999","DOI":"10.3389\/fmicb.2019.00999","article-title":"Mother-to-Child HTLV-1 transmission: Unmet research needs","volume":"10","author":"Rosadas","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Olindo, S., Jeannin, S., Saint-Vil, M., Signate, A., Edimonana-Kaptue, M., Joux, J., Merle, H., Richard, P., Granjeaud, S., and Cabre, P. (2018). Temporal trends in Human T-Lymphotropic virus 1 (HTLV-1) associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) incidence in Martinique over 25 years (1986\u20132010). PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006304"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.bjid.2018.02.002","article-title":"In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and\/or Human Immunodeficiency Virus type 1","volume":"22","author":"Assone","year":"2018","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1089\/aid.2011.0192","article-title":"Short communication: Human lymphotropic virus type 1 coinfection modulates the synthesis of cytokines by peripheral blood mononuclear cells from HIV type 1-infected individuals","volume":"28","author":"Abrahao","year":"2012","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S1413-8670(11)70132-5","article-title":"Coinfection by HTLV-I\/II is associated with an increased risk of strongyloidiasis and delay in starting antiretroviral therapy for AIDS patients","volume":"15","author":"Brites","year":"2011","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_13","unstructured":"Brites, C., Miranda, F., Luz, E., and Netto, E.M. (2019). Early and successful cART normalizes survival time in HIV-HTLV-1 coinfected patients. Clin. Infect. Dis., ciz756."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Van Tienen, C., Schim van der Loeff, M., Peterson, I., Cotten, M., Andersson, S., Holmgren, B., Vincent, T., de Silva, T., Rowland-Jones, S., and Aaby, P. (2011). HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029026"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1349-7006.1994.tb02087.x","article-title":"Mortality among inhabitants of an HTLV-I endemic area in Japan","volume":"85","author":"Iwata","year":"1994","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1016\/j.ijid.2009.11.040","article-title":"Higher mortality in HIV-2\/HTLV-1 co-infected patients with pulmonary tuberculosis in Guinea-Bissau, West Africa, compared to HIV-2-positive HTLV-1-negative patients","volume":"14","author":"Norrgren","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1742-4690-4-85","article-title":"Mortality associated with HIV-1, HIV-2, and HTLV-I single and dual infections in a middle-aged and older population in Guinea-Bissau","volume":"4","author":"Holmgren","year":"2007","journal-title":"Retrovirology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/QAI.0b013e3181cc5481","article-title":"Increased all-cause and cancer mortality in HTLV-II infection","volume":"54","author":"Biswas","year":"2010","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Einsiedel, L., Pham, H., Wilson, K., Walley, R., Turpin, J., Bangham, C., Gessain, A., and Woodman, R.J. (2018). Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006281"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1473-3099(19)30402-5","article-title":"Association between HTLV-1 infection and adverse health outcomes: A systematic review and meta-analysis of epidemiological studies","volume":"20","author":"Schierhout","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.virusres.2017.11.010","article-title":"Polymorphisms in HLA-C and KIR alleles are not associated with HAM\/TSP risk in HTLV-1-infected subjects","volume":"244","author":"Assone","year":"2018","journal-title":"Virus Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/jmv.20775","article-title":"Molecular characterization of human T-cell lymphotropic virus type 2 (HTLV-II) from people living in urban areas of Sao Paulo city: Evidence of multiple subtypes circulation","volume":"79","author":"Novoa","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014A metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J. BioMed. Inform."},{"key":"ref_24","first-page":"548","article-title":"Guide of clinical management of HTLV patient: Neurological aspects","volume":"63","author":"Araujo","year":"2005","journal-title":"Rquivos Neuro-Psiquiatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.3389\/fmicb.2018.01651","article-title":"Proposal of classification criteria for HTLV-1-associated myelopathy\/tropical spastic paraparesis disease activity","volume":"9","author":"Sato","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Haziot, M.E., Gascon, M.R., Assone, T., Fonseca, L.A.M., Luiz, O.D.C., Smid, J., Paiva, A.M., Marcusso, R., de Oliveira, A.C.P., and Casseb, J. (2019). Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0006967"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bellon, M., and Nicot, C. (2017). Telomere dynamics in immune senescence and exhaustion triggered by chronic viral infection. Viruses, 9.","DOI":"10.3390\/v9100289"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bjid.2018.07.003","article-title":"The impact of urinary incontinence on the quality of life and on the sexuality of patients with HAM\/TSP","volume":"22","author":"Gascon","year":"2018","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1023\/B:CACO.0000003853.82298.96","article-title":"Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: A prospective cohort study","volume":"14","author":"Arisawa","year":"2003","journal-title":"Cancer Causes Control"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1136\/jnnp.2009.191239","article-title":"A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK","volume":"81","author":"Martin","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ucl.2015.05.006","article-title":"Urinary tract infection and neurogenic bladder","volume":"42","author":"McKibben","year":"2015","journal-title":"Urol Clin. N. Am."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1111\/iwj.13110","article-title":"Spasticity and dementia increase the risk of pressure ulcers","volume":"16","author":"Jaul","year":"2019","journal-title":"Int. Wound J."},{"key":"ref_33","first-page":"26","article-title":"A Retrospective study of the impact of pressure ulcers on survival in elderly persons with chronic diseases","volume":"63","author":"Jaul","year":"2017","journal-title":"Ostomy Wound Manag."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/iwj.12086","article-title":"Systemic factors and mortality in elderly patients with pressure ulcers","volume":"12","author":"Jaul","year":"2015","journal-title":"Int. Wound J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1590\/S1677-5538.IBJU.2013.06.13","article-title":"Association between urinary symptoms and quality of life in HTLV-1 infected subjects without myelopathy","volume":"39","author":"Andrade","year":"2013","journal-title":"Int. Braz. J. Urol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1089\/aid.2017.0106","article-title":"Is it possible to control HIV infection in a middle-income country through a multidisciplinary approach?","volume":"34","author":"Casseb","year":"2018","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/QAD.0000000000002140","article-title":"albumin, white blood cell count, and body mass index improve discrimination of mortality in HIV-positive individuals","volume":"33","author":"Tate","year":"2019","journal-title":"AIDS"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1080\/17441692.2019.1616800","article-title":"Health inequalities and well-being in times of financial and political crisis in Brazil, a case study","volume":"14","year":"2019","journal-title":"Glob. Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e018545","DOI":"10.1136\/bmjopen-2017-018545","article-title":"Identifying socioeconomic, epidemiological and operational scenarios for tuberculosis control in Brazil: An ecological study","volume":"8","author":"Pelissari","year":"2018","journal-title":"BMJ Open"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0140-6736(18)30974-7","article-title":"Time to eradicate HTLV-1: An open letter to WHO","volume":"391","author":"Martin","year":"2018","journal-title":"Lancet"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:58Z","timestamp":1760190358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,26]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["pathogens9010025"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9010025","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,26]]}}}