Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load
Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and th...
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| Published in | PLoS neglected tropical diseases Vol. 13; no. 5; p. e0006967 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.05.2019
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| Abstract | Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL).
175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH).
After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS.
We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. |
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| AbstractList | Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL).Methods175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH).ResultsAfter the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS.ConclusionsWe found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). Methods: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). Results: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. Conclusions: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL).Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL).175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH).METHODS175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH).After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS.RESULTSAfter the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS.We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.CONCLUSIONSWe found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). Methods: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases “Emilio Ribas”, São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). Results: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. Conclusions: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome. At least 5–10 million people live with the Human T-Cell Lymphotropic Virus type 1 (HTLV-1) worldwide, and around 0.25–5% of them may develop HTLV-1-associated myelopathy/Tropical spastic paraparesis (HAM/TSP), which is associated with chronic inflammation. In this study, involving 175 HTLV-1-infected subjects originally classified as asymptomatic, we found that 42 of them in reality presented some early clinical conditions, including alterations related not only to the neurological system, but also to the eyes and the skin. We called such conditions intermediate syndrome. Thus, it seems reasonable to suggest that all HTLV-1-infected subjects should be monitored for symptoms that may arise earlier in the course of their infection. |
| Audience | Academic |
| Author | Haziot, Michel E. Casseb, Jorge Fonseca, Luiz Augusto M. Gascon, M. Rita Assone, Tatiane Luiz, Olinda do Carmo Marcusso, Rosa Maria do N. de Oliveira, A. C. Penalva Smid, Jerusa Paiva, Arthur M. |
| AuthorAffiliation | 4 Department of Preventive Medicine, University of São Paulo Medical School, São Paulo, Brazil 3 Institute of Tropical Medicine of São Paulo, São Paulo, SP, Brazil 1 Institute of Infectious Diseases “Emilio Ribas” (IIER) of São Paulo, São Paulo, SP, Brazil University of Washington, UNITED STATES 2 Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, University of São Paulo Medical School, Brazil |
| AuthorAffiliation_xml | – name: 2 Laboratory of Dermatology and Immunodeficiencies, Department of Dermatology, University of São Paulo Medical School, Brazil – name: 3 Institute of Tropical Medicine of São Paulo, São Paulo, SP, Brazil – name: 1 Institute of Infectious Diseases “Emilio Ribas” (IIER) of São Paulo, São Paulo, SP, Brazil – name: University of Washington, UNITED STATES – name: 4 Department of Preventive Medicine, University of São Paulo Medical School, São Paulo, Brazil |
| Author_xml | – sequence: 1 givenname: Michel E. surname: Haziot fullname: Haziot, Michel E. – sequence: 2 givenname: M. Rita surname: Gascon fullname: Gascon, M. Rita – sequence: 3 givenname: Tatiane surname: Assone fullname: Assone, Tatiane – sequence: 4 givenname: Luiz Augusto M. surname: Fonseca fullname: Fonseca, Luiz Augusto M. – sequence: 5 givenname: Olinda do Carmo surname: Luiz fullname: Luiz, Olinda do Carmo – sequence: 6 givenname: Jerusa surname: Smid fullname: Smid, Jerusa – sequence: 7 givenname: Arthur M. surname: Paiva fullname: Paiva, Arthur M. – sequence: 8 givenname: Rosa Maria do N. surname: Marcusso fullname: Marcusso, Rosa Maria do N. – sequence: 9 givenname: A. C. Penalva surname: de Oliveira fullname: de Oliveira, A. C. Penalva – sequence: 10 givenname: Jorge orcidid: 0000-0002-4553-2559 surname: Casseb fullname: Casseb, Jorge |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31042700$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | COPYRIGHT 2019 Public Library of Science 2019 Haziot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2019 Haziot et al 2019 Haziot et al |
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| References_xml | – volume: 3 start-page: 388 year: 2012 ident: ref3 article-title: Epidemiological Aspects and World Distribution of HTLV-1 Infection publication-title: Front Microbiol doi: 10.3389/fmicb.2012.00388 – volume: 4 start-page: 113 year: 2004 ident: ref23 article-title: White matter injury mechanisms publication-title: Curr Mol Med doi: 10.2174/1566524043479220 – volume: 20 start-page: 161 year: 2002 ident: ref8 article-title: Prevalence of HTLV-I Tax in a subset of patients with rheumatoid arthritis publication-title: Clin Exp Rheumatol – volume: 38 start-page: 1643 year: 2005 ident: ref19 article-title: Human T-cell lymphotropic virus type I (HTLV-I) proviral DNA viral load among asymptomatic patients and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis publication-title: Braz J Med Biol Res doi: 10.1590/S0100-879X2005001100011 – volume: 126 start-page: 515 year: 2003 ident: ref22 article-title: Axonal damage: a key predictor of outcome in human CNS diseases publication-title: Brain doi: 10.1093/brain/awg061 – volume: 18 start-page: 109 year: 2000 ident: ref2 article-title: Global epidemic of human T-cell lymphotropic virus type-I (HTLV-I) publication-title: J Emerg Med doi: 10.1016/S0736-4679(99)00173-0 – volume: 2 start-page: 49 year: 1987 ident: ref13 article-title: HTLV-I, brain abnormalities on magnetic resonance imaging, and relation with multiple sclerosis publication-title: Lancet doi: 10.1016/S0140-6736(87)93092-3 – volume: 13 start-page: S57 issue: Suppl 1 year: 1996 ident: ref9 article-title: HTLV-I arthropathy and Sjogren syndrome publication-title: J Acquir Immune Defic Syndr Hum Retrovirol doi: 10.1097/00042560-199600001-00011 – volume: 30 start-page: 780 year: 1992 ident: ref7 article-title: [Pathogenesis of T-lymphocyte alveolitis associated with HTLV-I infection] publication-title: Nihon Kyobu Shikkan Gakkai Zasshi – volume: 42 start-page: 377 year: 2009 ident: ref18 article-title: Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support publication-title: J Biomed Inform doi: 10.1016/j.jbi.2008.08.010 – volume: 2 start-page: 407 year: 1985 ident: ref4 article-title: Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis publication-title: Lancet doi: 10.1016/S0140-6736(85)92734-5 – volume: 23 start-page: 365 year: 2007 ident: ref12 article-title: Clinical manifestations associated with HTLV type I infection: a cross-sectional study publication-title: AIDS Res Hum Retroviruses doi: 10.1089/aid.2006.0140 – volume: 25 start-page: 532 year: 2002 ident: ref21 article-title: Axon pathology in neurological disease: a neglected therapeutic target publication-title: Trends Neurosci doi: 10.1016/S0166-2236(02)02255-5 – volume: 61 start-page: 49 year: 2015 ident: ref11 article-title: Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)-Infected Individuals Without HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study publication-title: Clin Infect Dis doi: 10.1093/cid/civ229 – volume: 63 start-page: 548 year: 2005 ident: ref16 article-title: [Guide of clinical management of HTLV patient: neurological aspects] publication-title: Arq Neuropsiquiatr – volume: 67 start-page: 132 year: 2009 ident: ref17 article-title: HTLV-1 and neurological conditions: when to suspect and when to order a diagnostic test for HTLV-1 infection? publication-title: Arq Neuropsiquiatr doi: 10.1590/S0004-282X2009000100036 – volume: 15 start-page: 419 year: 1986 ident: ref1 article-title: [Tropical spastic paraparesis in Martinique. 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| Title | Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load |
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