Abstract
Myelopathy associated with HTLV-1 infection or tropical spastic paraparesis (MAH / PET) is a chronic degenerative disease of the Central Nervous System that mainly affects the spinal cord. It is associated with infection by human lymphotropic virus type 1 (HTLV-1) that belongs to the Retroviridae family. Latin America, Asia and Sub-Saharan Africa are endemic areas of infection by HTLV-1 and MAH / PET between 2 % and 17 %, most asymptomatic. Colombia has a high prevalence and especially on its Pacific coast. In women, HTLV-1 infection is more prevalent than in men without the cause being clear, it is transmitted by blood transfusions (mainly whole blood), breastfeeding and / or sexual intercourse, which is the most common form of transmission in patients with MAH / PET. MAH / PET occurs mainly in adults, its incubation period until the development of symptoms varies from 2 years to decades. The main clinical manifestations of this disease are slowly progressive paraparesis and spasticity affecting gait, associated with sphincter symptoms, such as neurogenic bladder or constipation. For its diagnosis, magnetic resonance imaging (MRI) of the brain, spinal cord and the most used ELISA test are required with confirmation by western blot (WB). Currently there is no specific treatment for HAM / PET. In the future, the use of biomarkers will help early detection of the disease and even as a possible therapeutic target.
References
Bangham C, Araujo A, Yamano Y, Taylor GP. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat Rev Dis Primers. 2015;1:15012. doi: 10.1038/nrdp.2015.12.
Yamauchi J, Araya N, Yagishita N, Sato T, Yamano Y. An update on human T-cell leukemia virus type I (HTLV-l)-asso-ciated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers. Pharmacol Ther. 2020:107669. doi: 10.1016/j.pharmthera.2020.107669.
Kubota R. Pathogenesis of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Clin Expe Neuroimmunol. 2017;8(1):117-28. doi: 10.1111/cen3.12395.
Freedman A, Robertson P. Human T-lymphotropic virus type I: Virology, pathogenesis, and epidemiology. En: Bloom A (editor), UpToDate; 2020.
Matutes E. Adult T-cell leukaemia/lymphoma. J Clin Pathol. 2000;60(12): 1373-7. doi: 10.1136/jcp.2007.052456.
Durer C, Babiker HM. Adult T cell leukemia. [Actualizado 2020 Jun 30]. En: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.
Gessain A, Cassar O. Epidemiological Aspects and World distribution of HTLV-1 infection. Front Microbiol. 2012;3:388. doi:10.3389/fmicb.2012.00388.
European Centre for Disease Prevention and Control. Geographical distribution of areas with a high prevalence of HTLV-1 infection. Estocolmo: ECDC; 2015.
Borda M, Svibel G, Biglione M, Berini C. Hallazgo del virus linfotrópico T humano 1 (HTLV-1) subtipo Cosmopolita subgrupo Transcontinental (Aa) y del -2 subtipo b en donantes de sangre de Corrientes. Rev Argent Microbiol. 2019;51(4):307-15. doi: 10.1016/j.ram.2018.10.004.
Bermúdez Forero MI, Berrío Pérez M, Herrera Hernández AM, Rodríguez-Rodríguez MJ, García-Blanco S, Orjuela-Falla G, Beltrán M. Prevalencia de la infección con el virus linfotrópico de células T humanas de tipo 1 y 2 en donantes de sangre en Colombia, 2001-2014: implicaciones sobre la seguridad de la transfusión. Biomédica 2016;36(Supl 2):194200 doi:10.7705/biomedica.v36i0.2943.
Martin F, Fedina A, Youshya S, Taylor GP. A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK. J Neurol Neurosurg Psychiatry. 2010;81(12):1336-40. doi: 10.1136/jnnp.2009.191239.
Gessain A, Mahieux R. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological, and therapeutic aspects. Rev Neurol (Paris). 2012;168(3):257-69. doi: 10.1016/j.neurol.2011.12.006.
Kramer A, Maloney EM, Morgan OS, Rodgers-Johnson P, Manns A, Murphy EL, et al. Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica. Am J Epidemiol. 1995;142(11):1212-20. doi: 10.1093/oxfordjournals.aje.a117580.
Kendall EA, González E, Espinoza I, Tipismana M, Ver-donck K, Clark D, et al. Early neurologic abnormalities associated with human T-cell lymphotropic virus type 1 infection in a cohort of Peruvian children. J Pediatr. 2009;155(5):700-6. doi: 10.1016/j.jpeds.2009.05.027.
Chang Y, Kaidarova Z, Hindes D, Bravo M, Kiely N, Kamel H, et al. Seroprevalence and demographic determinants of human T-lymphotropic virus type 1 and 2 infections among first-time blood donors-United States, 2000-2009. J Infect Dis. 2014;209(4):523-31. doi: 10.1093/infdis/jit497.
Nozuma S, Jacobson S. Neuroimmunology of human T-lym-photropic virus type 1-associated myelopathy/tropical spastic paraparesis. Front Microbiol. 2019;10:885. doi: 10.3389/fmicb.2019.00885.
Saito M. Neuroimmunological aspects of human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis. J Neurovirol. 2014;20(2):164-74. doi: 10.1007/s13365-013-0192-8.
Goon PK, Hanon E, Igakura T, Tanaka Y, Weber JN, Taylor GP, Bangham CR. High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1-associated myelopathy/tropical spastic para-paresis. Blood. 2002;99(9):3335-41. doi: 10.1182/blood.v99.9.3335.
Toulza F, Nosaka K, Tanaka Y, Schioppa T, Balkwill F, Taylor GP, et al. Human T-lymphotropic virus type 1-induced CC chemokine ligand 22 maintains a high frequency of functional FoxP3+ regulatory T cells. J Immunol. 2010;185(1):183-9. doi: 10.4049/jimmunol.0903846.
Ando H, Sato T, Tomaru U, Yoshida M, Utsunomiya A, Yamauchi J, et al. Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy. Brain. 2013;136(Pt 9):2876-87. doi: 10.1093/brain/awt183.
Ijichi S, Izumo S, Eiraku N, Machigashira K, Kubota R, Nagai M, et al. An autoaggressive process against bystander tissues in HTLV-I-infected individuals: a possible pathomechanism of HAM/TSP. Med Hypotheses. 1993;41(6):542-7. doi: 10.1016/0306-9877(93)90111-3.
Moritoyo T, Reinhart TA, Moritoyo H, Sato E, Izumo S, Osame M, Haase AT. Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes. Ann Neurol. 1996;40(1):84-90. doi: 10.1002/ana.410400114.
Maloney EM, Cleghorn FR, Morgan OS, Rodgers-Johnson P, Cranston B, Jack N, et al. Incidence of HTLV-I-associat-ed myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad. J Acquir Immune Defic Syndr Hum Retroviral. 1998;17(2):167-70. doi: 10.1097/00042560199802010-00011.
Saeidi M, Sasannejad P, Foroughipour M, Shahami S, Shoeibi A. Prevalence of peripheral neuropathy in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Acta Neurol Belg. 2011;111(1):41-4.
Liesz A, Hähnel S, Korn K, et al. HTLV-1-associated my-elopathy/tropical spastic paraparesis: a differential diagnosis in multiple sclerosis. Nervenarzt. 2012;83(8):1028-34. doi: 10.1007/s00115-012-3565-y.
Cartón H. Mielopatías virales y no virales. En: Zaninovic V, De Castro Costa CM, editores. La PET/HAM - La paraparesia espástica tropical o mielopatía asociada con el HTLV-I. Cali: Fundación MAR-Colciencias; 1998. p. 1-11.
Castro-Costa CM, Carton H, Santos TJ. HTLV-I negative tropical spastic paraparesis: a scientific challenge. Arq Neuropsiquiatr. 2001;59(2-A):289-94. doi: 10.1590/s0004-282x2001000200031.
WHO virus diseases: human T-lymphotropic virus type I, HTLV-I. WHO Weekly Epidemiol Rec. 1989;49:382.
De Castro-Costa CM, Araújo AQ, Barreto MM, Takayanagui OM, Sohler MP, da Silva EL, et al. Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). AIDS Res Hum Retroviruses. 2006;22(10):931-5. doi: 10.1089/aid.2006.22.931.
Yao K, Hisada M, Maloney E, Yamano Y, Hanchard B, Wilks R, Rios M, Jacobson S. Human T lymphotropic virus types I and II western blot sero indeterminate status and its association with exposure to prototype HTLV-I. J Infect Dis. 2006;193(3):427-37. doi: 10.1086/499273.
Takenouchi N, Yamano Y, Usuku K, Osame M, Izumo S. Usefulness of proviral load measurement for monitoring of disease activity in individual patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J Neurovirol. 2003;9(1):29-35. doi: 10.1080/13550280390173418.
Cooper SA, van der Loeff MS, Taylor GP. The neurology of HTLV-1 infection. Pract Neurol. 2009;9(1):16-26. doi: 10.1136/jnnp.2008.167155.
Nakamura T. HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP): the role of HTLV-I-infected Th1 cells in the pathogenesis, and therapeutic strategy. Folia Neuropathol. 2009;47(2):182-94.
Izumo S, Goto I, Itoyama Y, Okajima T, Watanabe S, Kuroda Y, et al. Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial. Neurology. 1996;46(4):1016-21. doi: 10.1212/wnl.46.4.1016.
Oh U, Yamano Y, Mora CA, Ohayon J, Bagnato F, Butman JA, Dambrosia J, Leist TP, McFarland H, Jacobson S. Inter-feron-beta 1a therapy in human T-lymphotropic virus type I-associated neurologic disease. Ann Neurol. 2005;57(4):526-34. doi: 10.1002/ana.20429.
Araujo A, Bangham C, Casseb J, Gotuzzo E, Jacobson S, Martin F. International Retrovirology Association guidelines for the management of HTLV-1-associated myelopathy/ tropical spastic paraparesis; 2018. Disponible en: https://htlv.net/HAMpdf.
Lezin A, Gillet N, Olindo S, Signaté A, Grandvaux N, Verlaeten O, et al. Histone deacetylase mediated transcrip-tional activation reduces proviral loads in HTLV-1 associated myelopathy/tropical spastic paraparesis patients. Blood. 2007;110(10):3722-8. doi: 10.1182/blood-2007-04-085076.
Ureshino H, Kamachi K, Kimura S. Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19(6):326-31. doi: 10.1016/j.clml.2019.03.004.
Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, et al. Mogamulizumab (Anti-CCR4) in HTLV-1-as-sociated myelopathy. N Engl J Med. 2018;378(6):529-38. doi: 10.1056/NEJMoa1704827.
Dorsher PT, McIntosh PM. Neurogenic bladder. Adv Urol. 2012;2012:816274. doi: 10.1155/2012/816274.
Menezes SM, Decanine D, Brassat D, Khouri R, Schnitman SV, Kruschewsky R, et al. CD80+ and CD86+ B cells as biomarkers and possible therapeutic targets in HTLV-1 associated myelopathy/tropical spastic paraparesis and multiple sclerosis. J Neuroinflammation. 2014;11:18. doi: 10.1186/1742-2094-11-18.
Czuczman MS, Thall A, Witzig TE, Vose JM, Younes A, Emmanouilides C, et al. Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol. 2005;23(19):4390-8. doi: 10.1200/JCO.2005.09.018.

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