The Pathogenesis Of Tropical Spastic Paraparesis/human T-cell Leukemia Type I-associated Myelopathy

Tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy (TSP/HAM) is caused by a human T-cell leukemia virus type I (HTLV-I) after a long incubation period. TSP/HAM is characterized by a chronic progressive paraparesis with sphincter disturbances, no/mild sensory loss, the absence of spinal cord compression and seropositivity for HTLV-I antibodies. The pathogenesis of this entity is not completely known and involves a multivariable phenomenon of immune system activation against the presence of HTLV-I antigens, leading to an inflammatory process and demyelination, mainly in the thoracic spinal cord. The current hypothesis about the pathogenesis of TSP/HAM is: 1) presence of HTLV-I antigens in the lumbar spinal cord, noted by an increased DNA HTLV-I load; 2) CTL either with their lytic functions or release/production of soluble factors, such as CC-chemokines, cytokines, and adhesion molecules; 3) the presence of Tax gene expression that activates T-cell proliferation or induces an inflammatory process in the spinal cord; 4) the presence of B cells with neutralizing antibody production, or complement activation by an immune complex phenomenon, and 5) lower IL-2 and IFN-γ production and increased IL-10, indicating drive to a cytokine type 2 pattern in the TSP/HAM subjects and the existence of a genetic background such as some HLA haplotypes. All of these factors should be implicated in TSP/HAM and further studies are necessary to investigate their role in the development of TSP/HAM.331213951401Aboulafia, D.M., Clinical implications of human T-cell leukemia virus type I/II-associated diseases (1995) AIDS Reader, 5, pp. 118-125Uchiyama, T., Yodoi, J., Sagawa, K., Takatsuki, K., Uchino, H., Adult T-cell leukemia: Clinical and hematologic features of 16 cases (1977) Blood, 50, pp. 481-492Osame, M., Janssen, R., Kubota, H., Nishitani, H., Igata, A., Nagataki, S., Mori, M., Khabbaz, R., Nationwide survey of HTLV-I-associated myelopathy in Japan: Association with blood transfusion (1990) Annals of Neurology, 28, pp. 50-56Gessain, A., Barin, F., Vernant, J.C., Gout, O., Maurs, L., Calender, A., De The, G., Antibodies to human T-lyrnphotropic virus type-I in patients with tropical spastic paraparesis (1985) Lancet, 2, pp. 407-410Osame, M., Usuku, J., Izumo, S., Ijichi, N., Amitani, H., Igata, A., Matsumoto, M., Tara, M., HTLV-I-associated myelopathy: A new clinical entity (1985) Lancet, 1, pp. 1031-1032Gessain, A., Gout, O., Chronic myelopathy with human T-lymphotropic virus type I (HTLV-I) (1992) Annals of Internal Medicine, 117, pp. 933-946Iwasaki, Y., Pathology of chronic myelopathy associated with HTLV-I infection (TSP/HAM) (1990) Journal of Neurological Sciences, 96, pp. 103-123Seiki, M., Hattori, S., Hirayama, Y., Yoshida, M., Human adult T-cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA (1983) Proceedings of the National Academy of Sciences, USA, 80, pp. 3618-3622Murphy, E.L., Blattner, W.A., HTLV-I-associated leukemia: A model for chronic retroviral diseases (1988) Annals of Neurology, 23, pp. S174-S180Piccardo, P., Ceroni, M., Rodgers-Johnson, P., Mora, C., Asher, D.M., Char, G., Gibbs C.J., Jr., Gajdusek, D.C., Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica (1988) Annals of Neurology, 23, pp. 156-160Azizuki, S., Nakasato, O., Higuchi, Y., Tanabe, K., Setoguchi, M., Yoshida, S., Miyazaki, Y., Okajima, T., Necropsy findings in HTLV-I associated myelopathy (1987) Lancet, 1, pp. 156-157Tendler, G.L., Greenberg, S.J., Blattner, W.A., Manns, A., Murphy, E., Fleisher, T., Hanchard, B., Waldmann, T.A., Transactivation of mterleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: Pathogenic implications and a rationale for immunotherapy (1990) Proceedings of the National Academy of Sciences, USA, 87, pp. 5218-5222Cheng, H., Tranok, J., Parks, W.P., Human immunodeficiency virus type 1 genome activation induced by human T-cell leukemia virus type 1 tax protein is through cooperation of NF-kB and tat (1998) Journal of Virology, 72, pp. 6911-6916Gessain, A., Saal, F., Gout, O., Daniel, M.T., Flandrin, G., De The, G., Peries, J., Sigaux, F., High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis (1990) Blood, 75, pp. 428-433Nagai, M., Usuku, K., Matsumoto, W., Kodama, D., Takenouchi, T.M., Hashiguchi, S., Ichinose, M., Osame, M., Analysis of HTLV-I proviral load in 202 TSP/HAM patients and 243 asymptomatic HTLV-I carriers: High proviral load strongly predisposes to TSP/HAM (1998) Journal of Neurovirology, 4, pp. 586-593Manns, A., Miley, J.W., Wilks, J.R., Morgan, O.C., Hanchard, B., Warfe, G., Cranston, B., Waters, D., Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection (1999) Journal of Infectious Diseases., 180, pp. 1487-1493Hara, H., Autoimmune mechanism in TSP/HAM (1994) Nippon Rinsho, 52, pp. 2919-2925Levin, M.C., Krichavsky, M., Berk, J., Foley, S., Rosenfeld, M., Dalmau, J., Chang, G., Jacobson, S., Neuronal molecular mimicry in immune-mediated neurologic disease (1998) Annals of Neurology, 44, pp. 87-98Hoffman, T.L., Doms, R.W., Chemokines and coreceptors in HIV/SIV-host interactions (1998) AIDS, 12 (SUPPL. 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The pathogenesis of tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy

Tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy (TSP/HAM) is caused by a human T-cell leukemia virus type I (HTLV-I) after a long incubation period. TSP/HAM is characterized by a chronic progressive paraparesis with sphincter disturbances, no/mild sensory loss, the absence of spinal cord compression and seropositivity for HTLV-I antibodies. The pathogenesis of this entity is not completely known and involves a multivariable phenomenon of immune system activation against the presence of HTLV-I antigens, leading to an inflammatory process and demyelination, mainly in the thoracic spinal cord. The current hypothesis about the pathogenesis of TSP/HAM is: 1) presence of HTLV-I antigens in the lumbar spinal cord, noted by an increased DNA HTLV-I load; 2) CTL either with their lytic functions or release/production of soluble factors, such as CC-chemokines, cytokines, and adhesion molecules; 3) the presence of Tax gene expression that activates T-cell proliferation or induces an inflammatory process in the spinal cord; 4) the presence of B cells with neutralizing antibody production, or complement activation by an immune complex phenomenon, and 5) lower IL-2 and IFN-gamma production and increased IL-10, indicating drive to a cytokine type 2 pattern in the TSP/HAM subjects and the existence of a genetic background such as some HLA haplotypes. All of these factors should be implicated in TSP/HAM and further studies are necessary to investigate their role in the development of TSP/HAM

Prevalence Of Anxiety, Depression And Quality Of Life In Htlv-1 Infected Patients

The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. Objective: The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. Material and Methods: This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame's Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. Results: The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. Conclusion: A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients. © 2011 Elsevier Editora Ltda.156578582Carvalho, S.M.F., Oliveira, M.S.P., Thuler, L.C.S., HTLV-I and HTLVII infections in hematologic disorders patients, cancer patients and healthy individuals from Rio de Janeiro, Brazil (1997) J Aids Human Retrovirol, 15, pp. 238-242Carneiro-Proetti, A.B.F., Ribas, J.G.R., Catalan-Soares, B.C., Infecção e doença pelos vírus linfotrópicos humanos de células T (HTLV-I/II) no Brasil (2002) Rev Soc Bras Med Trop, 35 (5), pp. 499-508Castro, N.M., Rodrigues, W., Freitas, D.M., Urinary symptoms associated with human T-lymphtropic virus type I infection: evidence of urinary manifestations in large group of HTLV-I carriers (2007) Adult Urology, 69, pp. 813-818Osame, M., Usuku, K., Izumo, S., HTLV1 associated mielopathy, a new clinical entity (1986) Lancet, 1, pp. 1031-1032(2004), Brasil. Ministério da Saúde/Secretaria de Políticas de Saúde, Coordenação Nacional de DST e Aids. Guia do manejo clínico do pacientes com HTLV. Brasília;Catalan-Soares, B.C., Proietti, F.A., Carneiro-Proietti, A.B.F., Os vírus linfotrópicos de células T humanos (HTLV) na última década (1990-2000): Aspectos epidemiológicos (2001) Rev Bras Epidemiol, 4 (2), pp. 81-95Casseb, J., Oliveira, A.C.P., (2007), http://www.htlv.com.br/, Prevalência de HTLV I -II. [cited 09 Dec]. Available from: Dourado, I., Alcântara, L.C.J., Barreto, M.L., HTLV-I in the general population of Salvador, Brazil: A city with African ethnic and sociodemografic characteristics (2008) J AIDS, 34 (5), pp. 527-531Etzel, A., Infecção pelos vírus linfotrópicos de células T humanas dos tipos I (HTLV-I) e II (HTLV-II) em portadores de HIV em Santos - São Paulo: estudo de prevalência e fatores de risco (1999) Rev Soc Bras Med Trop, 32 (6), pp. 735-736Galvão-Castro, B., Loures, L., Rodrigues, L.G., Distribution of human T-lymphotropic virus type I among blood donorsa nationwide Brazilian study (1997) Transfusion, 37, pp. 242-243Proietti, F.A., Carneiro Proietti, A.C.F., Catalan-Soares Murphy, E., Global epidemiology of HTLV-1 infection and associated diseases (2005) Oncogene, 24, pp. 6058-6068Stumpf, B.P., Catalan-Soares, B., Carneiro-Proietti, A.B., Depression in HTLV-1 infected individuals: initial reports from the GIPH cohort in Belo Horizonte (2005) Brazil. AIDS Res Human Retroviruses, 21, pp. 465-476Souza, A.R.M., Frequency of major depressive disorder in HTLVI infected patients (2009) Arq. Neuro-Psiquiatr, 67 (2), pp. 365-366Carvalho, A.G.J., Galvão-Phileto, A.V., Lima, N.S., Frequency of mental disturbances in HTLV-1 patients in the state of Bahia, Brazil (2009) Braz J Infect Dis, 13 (1), pp. 5-8Shublaq, M.S., Avaliação da capacidade funcional e qualidade de vida em pacientes com mielopatia associada ao HTLV-I (2009), (MSc dissertation). Universidade Federal do Rio de JaneiroCoutinho, I.J., Lima, J., Galvão, B., Performance of activities of daily life for individuals with HAM/TSP: Interference in the quality of life (2008) Braz J Infect Dis, 12 (SUPPL. 1), p. 20Beck, A.T., Ward, C.H., Mendelson, M., An inventory for measuring depression (1961) Archof Gen Psychiatr, 4, pp. 53-63Cunha, J.A., Manual da versão em português das escalas de Beck (2001) Tradução e Adaptação Brasileira, , Casa do Psicólogo, São PauloFleck, M.P.A., Louzada, S., Xavier, M., Aplicação da versão em português do Instrumento Abreviado da Avaliação da Qualidade de Vida " WHOQOL -bref (2000) Rev Saúde Pública, 34 (2), pp. 178-183Dancey, C.P., Reidy, J., (2007) Estatística sem matemática para psicologia: usando SPSS para Windows, , Artmed, Porto AlegreNot

Clinical and epidemiological aspects of HTLV-II infection in São Paulo, Brazil: presence of Tropical Spastic Paraparesis/HTLV-Associated Myelopathy (TSP/HAM) simile diagnosis in HIV-1-co-infected subjects Aspectos clínicos e epidemiológicos da infecção pelo vírus linfotrópico de células T humanas do tipo 2 (HTLV-II) em São Paulo, Brasil: presença de paraparesia espástica tropical/mielopatia associada ao HTLV em pacientes co-infectados pelo HIV-1

In this study, the epidemiological and clinical features observed in solely HTLV-II-infected individuals were compared to those in patients co-infected with HIV-1. A total of 380 subjects attended at the HTLV Out-Patient Clinic in the Institute of Infectious Diseases "Emilio Ribas" (IIER), São Paulo, Brazil, were evaluated every 3-6 months for the last seven years by infectious disease specialists and neurologists. Using a testing algorithm that employs the enzyme immuno assay, Western Blot and polymerase chain reaction, it was found that 201 (53%) were HTLV-I positive and 50 (13%) were infected with HTLV-II. Thirty-seven (74%) of the HTLV-II reactors were co-infected with HIV-1. Of the 13 (26%) solely HTLV-II-infected subjects, urinary tract infection was diagnosed in three (23%), one case of skin vasculitis (8%) and two cases of lumbar pain and erectile dysfunction (15%), but none myelopathy case was observed. Among 37 co-infected with HIV-1, four cases (10%) presented with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile. Two patients showed paraparesis as the initial symptom, two cases first presented with vesical and erectile disturbances, peripheral neuropathies were observed in other five patients (13%), and seven (19%) patients showed some neurological signal or symptoms, most of them with lumbar pain (five cases). The results obtained suggest that neurological manifestations may be more frequent in HTLV-II/HIV-1-infected subjects than those infected with HTLV-II only.<br>Neste estudo, as características epidemiológicas e clínicas observadas nos indivíduos infectados pelo HTLV-II foram comparadas com os pacientes co-infectados com HIV-1. Um total de 380 indivíduos atendidos na clínica do Ambulatório HTLV do Instituto de Infectologia "Emilio Ribas" (IIER), São Paulo, Brasil, foram avaliados a cada 3-6 meses nos últimos sete anos por especialistas em doenças infecciosas e neurologistas. Usando um algoritmo que emprega ensaio imunoenzimático, Western Blot e reação em cadeia de polimerase, foram incluídos 201 (53%) pacientes infectados pelo HTLV-I e 50 (13%) infectados pelo HTLV-II. Trinta e sete (74%) eram co-infectados pelo HTLV-II e HIV-1. Dos 13 (26%) indivíduos unicamente infectados pelo HTLV-II, infecção do trato urinário foi diagnosticada em três, um com vasculite e em dois casos dor lombar e disfunção erétil mas nenhum caso de mielopatia foi observado. Entre 37 pacientes co-infectados com HIV-1, quatro (10%) casos apresentaram com paraparesia espástica tropical/mielopatia associada ao HTLV similar. Dois casos mostraram paraparesia como sintoma inicial, dois outros casos se apresentaram primeiramente com distúrbios vesical e erétil e as neuropatias periféricas foram observadas em cinco pacientes (13%). Outros sete (19%) pacientes mostraram algum sinal ou sintoma neurológico, a maioria deles com dor lombar (cinco casos). Os resultados sugerem que as manifestações neurológicas podem ser mais freqüentes em indivíduos co-infectados pelo HTLV-II/HIV-1 do que nos indivíduos infectados somente pelo HTLV-II