Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: infección por virus linfotrópico de células T humanas (HTLV)

Rosadas, Carolina; Brites, Carlos; Arakaki-Sánchez, Denise; Casseb, Jorge; Ishak, Ricardo

doi:10.1590/s1679-497420200006000015.esp1

Resumen

El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.

Palabras clave:
Enfermedades de Transmisión Sexual; Diagnóstico; Signos y Síntomas; Prevención de Enfermedades

Presentación

El artículo aborda la infección por el virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema que compone el Protocolo Clínico y Directrices Terapéuticas (PCDT) para Atención Integral a las Personas con Infecciones de Transmisión Sexual (ITS), publicado por la Secretaría de Vigilancia en Salud del Ministerio de Salud de Brasil. Para la elaboración del PCDT, se hizo una selección y análisis de las evidencias disponibles en la literatura y su discusión, durante un panel de especialistas. El documento fue aprobado por la Comisión Nacional de Incorporación de Tecnologías en el Sistema Único de Salud (Conitec),¹1. Ministério da Saúde (BR). Portaria MS/SCTIE no 42, de 5 de outubro de 2018. Torna pública a decisão de aprovar o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis (IST), no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2018 out 8 [citado 2020 out 15]; Seção I:88. Disponível em:https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/44303574/do1-2018-10-08-portaria-n-42-de-5-de-outubro-de-2018-44303438
https://www.in.gov.br/materia/-/asset_pu... siendo actualizado por el grupo técnico de especialistas en ITS en 2020.²2. Ministério da Saúde (BR). Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infeções sexualmente transmissíveis (IST) [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 jun 14]. Disponível em:http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes
http://www.aids.gov.br/pt-br/pub/2015/pr...

Aspectos epidemiológicos

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La infección por HTLV-1/2 resulta de la transmisión de linfocitos infectados, presentes en los fluidos corporales (sangre, semen, secreciones vaginales y leche materna), por transfusión de sangre y derivados, uso de drogas intravenosas, trasplante de órganos, sexo sin protección y por transmisión vertical. La transmisión vertical puede ocurrir a través de la placenta y, principalmente, a través de la lactancia materna.¹⁸18. Gessain A , Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol [Internet]. 2012 Nov [cited 2020 Oct 15] ; 3:388. Available from: https://dx.doi.org/10.3389%2Ffmicb.2012.00388
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https://doi.org/10.1002/ijc.2910510609... La carga proviral del HTLV-1 y el tiempo de exposición están relacionados con el aumento del riesgo de transmisión, especialmente durante las relaciones sexuales o la lactancia.²⁶26. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol [Internet]. 1998 Dec [cited 2020 Oct 15] ; 4(6):586-93. Available from: https://doi.org/10.3109/13550289809114225
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El contacto sexual es un medio importante de propagación de los virus HTLV-1 y HTLV-2 en áreas urbanas, rurales e indígenas.¹²12. Ishak R, Harrington WJ, Azevedo VN, Eiraku N, Ishak MO, Guerreiro JF, et al. Identification of human T cell lymphotropic virus type IIa infection in the Kayapo, an indigenous population of Brazil. AIDS Res Hum Retroviruses [Internet]. 1995 Jul [cited 2020 Oct 15] ; 11(7):813-21. Available from: https://doi.org/10.1089/aid.1995.11.813
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https://doi.org/10.1080/15321819.2019.16... sin embargo, entre las comunidades indígenas, la eficiencia de la transmisión no muestra diferencias entre los géneros^.¹²12. Ishak R, Harrington WJ, Azevedo VN, Eiraku N, Ishak MO, Guerreiro JF, et al. Identification of human T cell lymphotropic virus type IIa infection in the Kayapo, an indigenous population of Brazil. AIDS Res Hum Retroviruses [Internet]. 1995 Jul [cited 2020 Oct 15] ; 11(7):813-21. Available from: https://doi.org/10.1089/aid.1995.11.813
https://doi.org/10.1089/aid.1995.11.813... ^,²⁹29. Lairmore MD, Jacobson S, Gracia F, De BK, Castillo L, Larreategui M, et al. Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama. Proc Natl Acad Sci U S A [Internet]. 1990 Nov [cited 2020 Oct 15] ; 87(22):8840-4. Available from: https://dx.doi.org/10.1073%2Fpnas.87.22.8840
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https://doi.org/10.1186/s12879-019-4041-... La transmisión sexual está asociada con el sexo sin protección, la relación sexual con usuarios de drogas intravenosas y la presencia de otras ITS.³⁵35. Murphy EL , Figueroa JP, Gibbs WN, Brathwaite A, Holding-Cobham M, Waters D, et al. Sexual transmission of human T-lymphotropic virus type I (HTLV-I). Ann Intern Med [Internet]. 1989 Oct [cited 2020 Oct 15] ; 111(7):555-60. Available from: https://doi.org/10.7326/0003-4819-111-7-555
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HTLV-1 y HTLV-2 se distribuyen a escala mundial.¹⁸18. Gessain A , Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol [Internet]. 2012 Nov [cited 2020 Oct 15] ; 3:388. Available from: https://dx.doi.org/10.3389%2Ffmicb.2012.00388
https://doi.org/10.3389%2Ffmicb.2012.003... Brasil tiene frecuencias variables, entre 0,01 y 1,35% en la población general,²⁸28. Carneiro-Proietti ABF , Sabino EC, Leão S, Salles NA, Loureiro P, Sarr M, et al. Human T-lymphotropic virus type 1 and type 2 seroprevalence, incidence, and residual transfusion risk among blood donors in Brazil during 2007-2009. AIDS Res Hum Retroviruses [Internet]. 2012 Oct [cited 2020 Oct 15] ; 28(10):1265-72. Available from: https://doi.org/10.1089/aid.2011.0143
https://doi.org/10.1089/aid.2011.0143... ^,³⁸38. Galvão-Castro B, Loures L, Rodriques LG, Sereno A, Ferreira Júnior OC, Franco LG, et al. Distribution of human T-lymphotropic virus type I among blood donors: a nationwide Brazilian study. Transfusion [Internet]. 1997 Feb [cited 2020 Oct 15] ; 37(2):242-3. Available from: https://doi.org/10.1046/j.1537-2995.1997.37297203532.x
https://doi.org/10.1046/j.1537-2995.1997... ^,³⁹39. Ishak R , Ishak MO, Vallinoto ACR . The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil. Retrovirology [Internet]. 2020 Feb [cited 2020 Oct 15] ; 17:4. Available from: https://dx.doi.org/10.1186%2Fs12977-020-0512-z
https://doi.org/10.1186%2Fs12977-020-051... según el área geográfica y los factores de riesgo conductual.¹²12. Ishak R, Harrington WJ, Azevedo VN, Eiraku N, Ishak MO, Guerreiro JF, et al. Identification of human T cell lymphotropic virus type IIa infection in the Kayapo, an indigenous population of Brazil. AIDS Res Hum Retroviruses [Internet]. 1995 Jul [cited 2020 Oct 15] ; 11(7):813-21. Available from: https://doi.org/10.1089/aid.1995.11.813
https://doi.org/10.1089/aid.1995.11.813... ^,¹⁸18. Gessain A , Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol [Internet]. 2012 Nov [cited 2020 Oct 15] ; 3:388. Available from: https://dx.doi.org/10.3389%2Ffmicb.2012.00388
https://doi.org/10.3389%2Ffmicb.2012.003... ^,⁴⁰40. Einsiedel L, Woodman RJ, Flynn M, Wilson K, Cassar O , Gessain A . Human T-lymphotropic virus type 1 infection in an indigenous Australian population: epidemiological insights from a hospital-based cohort study. BMC Public Health [Internet]. 2016 Aug [cited 2020 Oct 15] ; 16:787. Available from: https://doi.org/10.1186/s12889-016-3366-5
https://doi.org/10.1186/s12889-016-3366-... ^,⁴¹41. Paiva AM, Assone T, Haziot MEJ, Smid J, Fonseca LAM, Luiz OC, et al. Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring. Sci Rep [Internet]. 2018 [cited 2020 Oct 15] ; 8:7742. Available from: https://doi.org/10.1038/s41598-018-25939-y
https://doi.org/10.1038/s41598-018-25939... Los grupos con mayor vulnerabilidad a la infección por ambos virus incluyen (i) usuarios de drogas intravenosas, (ii) profesionales del sexo, (iii) hombres que tienen sexo con hombres, (iv) individuos sometidos a transfusiones de sangre antes de 1993 y (v) parejas sexuales que se sabe que tienen HTLV. La disminución de la prevalencia de HTLV-1 entre los donantes de sangre a lo largo de los años²⁸28. Carneiro-Proietti ABF , Sabino EC, Leão S, Salles NA, Loureiro P, Sarr M, et al. Human T-lymphotropic virus type 1 and type 2 seroprevalence, incidence, and residual transfusion risk among blood donors in Brazil during 2007-2009. AIDS Res Hum Retroviruses [Internet]. 2012 Oct [cited 2020 Oct 15] ; 28(10):1265-72. Available from: https://doi.org/10.1089/aid.2011.0143
https://doi.org/10.1089/aid.2011.0143... ^,³⁸38. Galvão-Castro B, Loures L, Rodriques LG, Sereno A, Ferreira Júnior OC, Franco LG, et al. Distribution of human T-lymphotropic virus type I among blood donors: a nationwide Brazilian study. Transfusion [Internet]. 1997 Feb [cited 2020 Oct 15] ; 37(2):242-3. Available from: https://doi.org/10.1046/j.1537-2995.1997.37297203532.x
https://doi.org/10.1046/j.1537-2995.1997... es una situación privilegiada en Brasil, promovida desde 1993⁴²42. Brasil. Ministério da Saúde. Portaria GM/MS n. 1376, de 19 de novembro de 1993. Aprova alterações na Portaria no 721/GM, de 09.08.89, que aprova Normas Técnicas para coleta, processamento e transfusão de sangue, componentes e derivados, e dá outras providências [Internet]. Diário Oficial da União , Brasília (DF), 1993 dez 2 [citado 2020 out 15]; Seção I:18405. Disponível em: http://redsang.ial.sp.gov.br/site/docs_leis/ps/ps29.pdf
http://redsang.ial.sp.gov.br/site/docs_l... con la regulación del cribado obligatorio de sangre y hemoderivados.

Los estudios seroepidemiológicos para HTLV-1/2 se basan en la detección de anticuerpos específicos. Es importante enfatizar que pocos estudios poblacionales se han realizado adecuadamente, con una gran parte de la información epidemiológica sobre HTLV-1/2 proveniente de estudios antiguos, que a menudo no definen adecuadamente las tasas de incidencia y prevalencia, muestran resultados contradictorios y no permiten la definición de medidas de prevención y control ajustadas.¹⁸18. Gessain A , Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol [Internet]. 2012 Nov [cited 2020 Oct 15] ; 3:388. Available from: https://dx.doi.org/10.3389%2Ffmicb.2012.00388
https://doi.org/10.3389%2Ffmicb.2012.003... ^,³⁹39. Ishak R , Ishak MO, Vallinoto ACR . The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil. Retrovirology [Internet]. 2020 Feb [cited 2020 Oct 15] ; 17:4. Available from: https://dx.doi.org/10.1186%2Fs12977-020-0512-z
https://doi.org/10.1186%2Fs12977-020-051...

El HTLV-2, considerado una infección ancestral, aparentemente se adapta bien al ser humano, con raras manifestaciones clínicas.⁵5. Kalyanaraman VS , Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC . A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science [Internet]. 1982 Nov [cited 2020 Oct 15]; 218(4572):571-3. Available from: https://doi.org/10.1126/science.6981847
https://doi.org/10.1126/science.6981847... ^,⁴³43. Hjelle B, Appenzeller O, Mills R, Appenzeller O, Jahnke R, Alexander S, et al. Chronic neurodegenerative disease associated with HTLV-II infection. Lancet [Internet]. 1992 Mar [cited 2020 Oct 15] ; 339(8794):645-6. Available from: https://doi.org/10.1016/0140-6736(92)90797-7
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44. Zucker-Franklin D, Hooper WC, Evatt BL. Human lymphotropic retroviruses associated with mycosis fungoides: evidence that human T-cell lymphotropic virus type II (HTLV-II) as well as HTLV-I may play a role in the disease. Blood [Internet]. 1992 Sep [cited 2020 Oct 15] ; 80(6):1537-45. Available from: https://pubmed.ncbi.nlm.nih.gov/1520878 /
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45. Maytal J, Horowitz S, Lipper S, Poiesz B, Wang CY, Siegal FP. Progressive nemaline rod myopathy in a woman coinfected with HIV-1 and HTLV-2. Mt Sinai J Med. 1993 May; 60(3):242-6.

46. Peters AA, Oger JJ, Coulthart MB, Waters DJ, Cummings HJ, Dekaban GA. An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation. J Clin Virol [Internet]. 1999 Sep [cited 2020 Oct 15] ; 14(1):37-50. Available from: https://doi.org/10.1016/S1386-6532(99)00041-4
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47. Araujo A, Hall WW . Human T-Lymphotropic virus type ii and neurological disease. Ann Neurol [Internet]. 2004 Jul [cited 2020 Oct 15] ; 56(1):10-9. Available from: https://doi.org/10.1002/ana.20126
https://doi.org/10.1002/ana.20126... ^-⁴⁸48. Rosadas C , Vicente ACP, Zanella L, Cabral-Castro MJ, Peralta JM, Puccioni-Sohler M. Human T-lymphotropic virus type 2 subtype b in a patient with chronic neurological disorder. J Neurovirol [Internet]. 2014 Dec [cited 2020 Oct 15] ; 20(6):636-9. Available from: https://doi.org/10.1007/s13365-014-0280-4
https://doi.org/10.1007/s13365-014-0280-... El HTLV-2, de hecho, se suele utilizar como marcador de la migración humana, desde la salida de las primeras poblaciones del continente africano.⁴⁹49. Black FL. Tracing prehistoric migrations by the viruses they carry: human T-cell lymphotropic viruses as markers of ethnic relationships. Hum Biol. 1997 Aug; 69(4):467-82.^,⁵⁰50. Ishak R , Machado LFA, Cayres-Vallinoto I, GuimarãesIshak MO , Vallinoto ACR . Infectious agents as markers of human migration toward the Amazon Region of Brazil. Front Microbiol [Internet]. 2017 Aug [cited 2020 Oct 15] ; 8:1663. Available from: https://dx.doi.org/10.3389%2Ffmicb.2017.01663
https://doi.org/10.3389%2Ffmicb.2017.016...

Aspectos clínicos

Los retrovirus se integran con el ácido nucleico en la célula infectada y establecen la persistencia viral, lo que lleva al mantenimiento del virus y a los diferentes resultados de la infección. El HTLV-1 está asociado con un linfoma agresivo, la enfermedad llamada leucemia/linfoma de células T adultas (adult T cell leukemia/lymphoma, ATLL),⁵¹51. Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, et al. Treatment and survival among 1594 patients with ATL. Blood [Internet]. 2015 Dec [cited 2020 Oct 15] ; 126(24):2570-7. Available from: https://doi.org/10.1182/blood-2015-03-632489
https://doi.org/10.1182/blood-2015-03-63... ^,⁵²52. Taniguchi H, Imaizumi Y, Takasaki Y, Nakashima J, Kato T, Itonaga H, et al. Clinical features at transformation in adult T-cell leukemia-lymphoma with smoldering and chronic types. Int J Hematol [Internet]. 2019 Apr [cited 2020 Oct 15] ; 109(4):402-8. Available from: https://doi.org/10.1007/s12185-019-02602-4
https://doi.org/10.1007/s12185-019-02602... y a una enfermedad neurodegenerativa, mielopatía asociada con HTLV-1 (HTLV-1 associated myelopathy, HAM).⁵³53. Rodgers-Johnson P, Gajdusek DC, Morgan OS, Zaninovic V, Sarin PS, Graham DS. HTLV-I and HTLV-III antibodies and tropical spastic paraparesis. Lancet (London, England) [Internet]. 1985 Oct [cited 2020 Oct 15] ; 2(8466):1247-8. Available from: https://doi.org/10.1016/s0140-6736(85)90778-0
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54. Osame M, Usuku K , Izumo S, Ijichi N, Amitani H, Igata A, et al. HTLV-I associated myelopathy, a new clinical entity. Lancet [Internet]. 1986 May [cited 2020 Oct 15] ; 1(8488):1031-2. Available from: https://doi.org/10.1016/s0140-6736(86)91298-5
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55. Araujo A Update on neurological manifestations of HTLV-1 infection. Curr Infect Dis Rep [Internet]. 2015 Feb [cited 2020 Oct 15] ; 17(2):459. Available from: https://doi.org/10.1007/s11908-014-0459-0
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56. Bangham CRM, Araujo A , Yamano Y, Taylor GP . HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat Rev Dis Primers [Internet]. 2015 Jun [cited 2020 Oct 15] ; 1:15012. Available from: https://doi.org/10.1038/nrdp.2015.12
https://doi.org/10.1038/nrdp.2015.12... ^-⁵⁷57. Nozuma S, Jacobson S. Neuroimmunology of human T-Lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Front Microbiol [Internet]. 2019 Apr [cited 2020 Oct 15] ; 10:885. Available from: https://dx.doi.org/10.3389%2Ffmicb.2019.00885
https://doi.org/10.3389%2Ffmicb.2019.008...

La infección por HTLV-1 muestra una amplia variedad de interacciones con el huésped humano y se han reconocido importantes manifestaciones clínicas en los ojos,⁵⁸58. Chew R, Henderson T, Aujla J, Whist E, Einsiedel L . Turning a blind eye: HTLV-1-associated uveitis in Indigenous adults from Central Australia. Int Ophthalmol [Internet]. 2018 Oct [cited 2020 Oct 15] ; 38(5):2159-62. Available from: https://doi.org/10.1007/s10792-017-0659-3
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59. Nakao K, Abematsu N, Sakamoto T. Systemic diseases in patients with HTLV-1-associated uveitis. Br J Ophthalmol [Internet]. 2018 Mar [cited 2020 Oct 15] ; 102(3):373-6. Available from: https://doi.org/10.1136/bjophthalmol-2017-310658
https://doi.org/10.1136/bjophthalmol-201...

60. Kamoi K, Okayama A, Izumo S , Hamaguchi I, Uchimaru K, Tojo A, et al. Tackling HTLV-1 infection in ophthalmology: a nationwide survey of ophthalmic care in an endemic country, Japan. Br J Ophthalmol [Internet]. 2020 Mar [cited 2020 Oct 15] . Available from: https://doi.org/10.1136/bjophthalmol-2019-315675
https://doi.org/10.1136/bjophthalmol-201... ^-⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... piel,⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... ^,⁶²62. Bimbi C, Brzezinski P, Sokolowska-Wojdylo M. Crusted (Norwegian) scabies as a strong marker of adult T-cell leukemia/lymphoma in HTLV-1 infection. Clin Case Reports [Internet]. 2019 Mar [cited 2020 Oct 15] ; 7(3):474-6. Available from: https://dx.doi.org/10.1002%2Fccr3.1983
https://doi.org/10.1002%2Fccr3.1983... pulmón,⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... ^,⁶³63. Magno Falcão LF, Falcão ASC, Medeiros Sousa RC, Vieira WB, Oliveira RTM, Normando VMF, et al. CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon. PLoS One [Internet]. 2017 Nov [cited 2020 Oct 15] ; 12(11):e0186055. Available from: https://doi.org/10.1371/journal.pone.0186055
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64. Dias ARN, Falcão LFM, Falcão ASC, Normando VMF, Quaresma JAS. Human T lymphotropic virus and pulmonary diseases. Front Microbiol [Internet]. 2018 Aug [cited 2020 Oct 15] ; 9:1879. Available from: https://dx.doi.org/10.3389%2Ffmicb.2018.01879
https://doi.org/10.3389%2Ffmicb.2018.018... ^-⁶⁵65. Kako S, Joshita S, Matsuo A, Kawaguchi K, Umemura T, Tanaka E. A case of adult T-Cell leukemia/lymphoma complicated with bilateral chylothorax. Case Rep Oncol Med [Internet]. 2019 Feb [cited 2020 Oct 15] ; 2019:8357893. Available from: https://doi.org/10.1155/2019/8357893
https://doi.org/10.1155/2019/8357893... articulaciones,⁶⁶66. Nishioka K , Maruyama I, Sato K, Kitajima I, Nakajima Y, Osame M. Chronic inflammatory arthropathy associated with HTLV-I. Lancet [Internet]. 1989 Feb [cited 2020 Oct 15] ; 1(8635):441. Available from: https://doi.org/10.1016/s0140-6736(89)90038-x
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67. Sato K , Maruyama I , Maruyama Y, Kitajima I , Nakajima Y , Higaki M, et al. Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immunopathologic features. Arthritis Rheum [Internet]. 1991 Jun [cited 2020 Oct 15] ; 34(6):714-21. Available from: https://doi.org/10.1002/art.1780340612
https://doi.org/10.1002/art.1780340612... ^-⁶⁸68. Dennis G, Chitkara P. A case of human T lymphotropic virus type I-associated synovial swelling. Nat Clin Pract Rheumatol [Internet]. 2007 Nov [cited 2020 Oct 15] ; 3:675-80. Available from: https://doi.org/10.1038/ncprheum0648
https://doi.org/10.1038/ncprheum0648... tiroides,⁶⁹69. Kawai H, Inui T, Kashiwagi S, Tsuchihashi T, Masuda K, Kondo A, et al. HTLV-I infection in patients with autoimmune thyroiditis (Hashimoto’s thyroiditis). J Med Virol [Internet]. 1992 Oct [cited 2020 Oct 15] ; 38(2):138-41. Available from: https://doi.org/10.1002/jmv.1890380212
https://doi.org/10.1002/jmv.1890380212... ^,⁷⁰70. Matsuda T, Tomita M, Uchihara J-N, Okudaira T, Ohshiro K, Tomoyose T, et al. Human T cell leukemia virus type I-infected patients with Hashimoto’s thyroiditis and Graves’ disease. J Clin Endocrinol Metab [Internet]. 2005 Oct [cited 2020 Oct 15] ; 90(10):5704-10. Available from: https://doi.org/10.1210/jc.2005-0679
https://doi.org/10.1210/jc.2005-0679... corazón,⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... ^,⁷¹71. Abolbashari S, Darroudi S, Tayefi M, Khashyarmaneh Z, Zamani P, Haghighi HM, et al. Association between serum zinc and copper levels and antioxidant defense in subjects infected with human T-lymphotropic virus type 1. J Blood Med [Internet]. 2018 Dec [cited 2020 Oct 15] ; 10:29-35. Available from: https://doi.org/10.2147/jbm.s184913
https://doi.org/10.2147/jbm.s184913... ^,⁷²72. Mohammadi FS, Mosavat A, Shabestari M, Shabestari M, Ghezeldasht SA, Shabestari M, et al. HTLV-1-host interactions facilitate the manifestations of cardiovascular disease. Microb Pathog [Internet]. 2019 Sep [cited 2020 Oct 15] ; 134:103578. Available from: https://doi.org/10.1016/j.micpath.2019.103578
https://doi.org/10.1016/j.micpath.2019.1... intestino,⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... ^,⁷³73. Oliveira TSS, Andrade RCP, Santos DN, Orrico KF, Abraão Neto J, Oliveira CJV, et al. Prevalence of Bowel Symptoms in Patients Infected with Human T-Lymphotropic type 1 Virus. Rev Soc Bras Med Trop [Internet]. 2019 Nov [cited 2020 Oct 15] ; 52:e20180486. Available from: http://dx.doi.org/10.1590/0037-8682-0486-2018
https://doi.org/10.1590/0037-8682-0486-2... y vejiga,⁶¹61. Schierhout G, McGregor S, Gessain A , Einsiedel L , Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 20(1):133-43. Available from: https://doi.org/10.1016/s1473-3099(19)30402-5
https://doi.org/10.1016/s1473-3099(19)30... ^,⁷⁴74. Silva MT, Coutinho F, Leite AC, Harab RC, Araújo A, Andrada-Serpa MJ. Isolated bladder dysfunction in human T lymphotropic virus type 1 infection. Clin Infect Dis [Internet]. 2009 Feb [cited 2020 Oct 15] ; 48(3):e34-6. Available from: https://doi.org/10.1086/595855
https://doi.org/10.1086/595855... ^,⁷⁵75. Nayar S, Pawar B, Einsiedel L , Fernandes D, George P, Thomas S, et al. Isolated neurogenic bladder associated with human T-Lymphotropic virus type 1 infection in a renal transplant patient from central Australia: a case report. Transplant Proc [Internet]. 2018 Dec [cited 2020 Oct 15] ; 50(10):3940-2. Available from: https://doi.org/10.1016/j.transproceed.2018.08.031
https://doi.org/10.1016/j.transproceed.2... entre otros. El amplio espectro de enfermedades revela la complejidad clínica de la infección, por lo que requiere una atención multidisciplinar en el cuidado de los infectados.

No obstante el desenlace clínico de las infecciones por el HTLV-1 ser considerado bajo (5%), el número de casos clínicos asociados a la infección por el HTLV-1 puede alcanzar un nivel mayor, y aún precisa ser mejor definido.⁵⁵55. Araujo A Update on neurological manifestations of HTLV-1 infection. Curr Infect Dis Rep [Internet]. 2015 Feb [cited 2020 Oct 15] ; 17(2):459. Available from: https://doi.org/10.1007/s11908-014-0459-0
https://doi.org/10.1007/s11908-014-0459-... Manifestaciones clínicas intermediarias pueden ser frecuentes, antes que ocurra la HAM.⁷⁶76. Tanajura D, Castro N, Oliveira P, Abraão-Neto, MA, Carvalho NB, et al. 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. Clin Infect Dis [Internet]. 2015 Jul [cited 2020 Oct 15] ; 61(1):49-56. Available from: https://doi.org/10.1093/cid/civ229
https://doi.org/10.1093/cid/civ229... ^,⁷⁷77. Haziot ME, Gascon MR, Assone T, Fonseca LAM, Luiz OC, Smid J, et al. Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load. PLoS Negl Trop Dis [Internet]. 2019 May [cited 2020 Oct 15] ; 13:e0006967. Available from: https://doi.org/10.1371/journal.pntd.0006967
https://doi.org/10.1371/journal.pntd.000... La carga proviral en la infección por el HTLV-1 es importante en la progresión para la enfermedad,⁷⁸78. Yamano Y , Nagai M , Brennan M, Mora CA, Soldan SS, Tomaru U, et al. Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8+ T cells, and disease severity in HTLV-1-associated myelopathy (HAM/TSP). Blood [Internet]. 2002 Jan [cited 202 Oct 15]; 99(1):88-94. Available from: https://doi.org/10.1182/blood.v99.1.88
https://doi.org/10.1182/blood.v99.1.88... ^,⁷⁹79. Montanheiro PA, Oliveira ACP, Posada-Vergara MP, Milagres AC, Tauil C, et al. 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. Brazilian J Med Biol Res [Internet]. 2005 Nov [cited 2020 Oct 15] ; 38(11):1643-7. Available from: http://dx.doi.org/10.1590/S0100-879X2005001100011
https://doi.org/10.1590/S0100-879X200500... y es usualmente baja en los individuos asintomáticos cuando comparados a los que presentan enfermedades relacionadas al HTLV-1.

Mielopatía asociada al HTLV-1

La HAM se presenta en aproximadamente el 4% de los portadores de HTLV, aunque las manifestaciones clínicas pueden afectar a más del 10% de ellos.⁷⁷77. Haziot ME, Gascon MR, Assone T, Fonseca LAM, Luiz OC, Smid J, et al. Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load. PLoS Negl Trop Dis [Internet]. 2019 May [cited 2020 Oct 15] ; 13:e0006967. Available from: https://doi.org/10.1371/journal.pntd.0006967
https://doi.org/10.1371/journal.pntd.000... La HAM se manifiesta predominantemente en la cuarta y quinta décadas de la vida, siendo poco común antes de los 20 o después de los 70 años de edad. Suele comenzar de forma insidiosa y progresa lentamente, especialmente en mujeres: la incidencia de casos de HAM en mujeres es dos o tres veces superior a la observada en hombres. Las alteraciones de la marcha son consecuencia de la disminución progresiva de la fuerza muscular y la espasticidad de los miembros inferiores,⁸⁰80. Champs APS, Passos VMA, Barreto SM, Vaz LS, Ribas JGR. HTLV-1 associated myelopathy: clinical and epidemiological profile in a 10-year case series study. Rev Soc Bras Med Trop [Internet]. 2010 [cited 2020 Oct 15] ; 43(6):668-72. Available from: http://dx.doi.org/10.1590/S0037-86822010000600013
https://doi.org/10.1590/S0037-8682201000... lo que lleva a la necesidad, con el tiempo, de asistencia a la movilidad (con el apoyo de bastones y andadores), que puede evolucionar hacia el uso de silla de ruedas. El tiempo de evolución varía de meses a décadas. Los síntomas de disfunción vesico-intestinal y sexual pueden ser las quejas iniciales del individuo enfermo. Generalmente, la HAM se caracteriza por incontinencia de urgencia, estreñimiento y disfunción eréctil en la población masculina. La afección neurológica puede estar asociada a procesos multisistémicos, como dermatitis, uveítis, neumonía, además de alteraciones cognitivas.⁸¹81. Okajima R, Casseb J, Sanches JA. Co-presentation of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis and adult-onset infective dermatitis associated with HTLV-1 infection. Int J Dermatol [Internet]. 2013 Jan [cited 2020 Oct 15] ; 52(1):63-8. Available from: https://doi.org/10.1111/j.1365-4632.2012.05606.x
https://doi.org/10.1111/j.1365-4632.2012... ^,⁸²82. Okajima R, Oliveira ACP, Smid J , Casseb J, Sanches JA. High prevalence of skin disorders among HTLV-1 infected individuals independent of clinical status. PLoS Negl Trop Dis [Internet]. 2013 Nov [cited 2020 Oct 15] ; 7(11):e2546. Available from: https://dx.doi.org/10.1371%2Fjournal.pntd.0002546
https://doi.org/10.1371%2Fjournal.pntd.0... El diagnóstico de HAM es muy importante, su tratamiento precoz puede conducir a una respuesta terapéutica más eficaz⁸³83. Araujo AQC, Wedemann D. HTLV-1 Associated neurological complex. What is hidden below the water? AIDS Rev [Internet]. 2019 [cited 2020 Oct 15] ; 21(4):211-7. Available from: https://doi.org/10.24875/aidsrev.19000108
https://doi.org/10.24875/aidsrev.1900010... y de mejor pronóstico, cuando se instituye hasta cinco años después de los primeros síntomas.

Los niveles de carga proviral se correlacionan con la progresión de la enfermedad, especialmente con la debilidad muscular. Aunque la magnitud de la carga proviral en sangre periférica se asocia con HAM, no es el único factor diagnóstico o pronóstico de la patología.⁸⁴84. Matsuzaki T, Nakagawa M, Nagai M , Usuku K , Arimura K, Kubota H, et al. HTLV-I proviral load correlates with progression of motor disability in HAM/TSP: analysis of 239 HAM/TSP patients including 64 patients followed up for 10 years. J Neurovirol [Internet]. 2001 Jun [cited 2020 Oct 15] ; 7(3):228-34. Available from: https://doi.org/10.1080/13550280152403272
https://doi.org/10.1080/1355028015240327... En el LCR, la carga proviral puede ser importante para definir la progresión de HAM, ya que las células infectadas con HTLV- 1 en el sistema nervioso central aceleran el proceso inflamatorio local.²⁶26. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol [Internet]. 1998 Dec [cited 2020 Oct 15] ; 4(6):586-93. Available from: https://doi.org/10.3109/13550289809114225
https://doi.org/10.3109/1355028980911422... ^,⁸⁵85. Rosadas C , Puccioni-Sohler M . Relevance of retrovirus quantification in cerebrospinal fluid for neurologic diagnosis. J Biomed Sci [Internet]. 2015 Aug [cited 2020 Oct 15] ; 22(1):66. Available from: https://doi.org/10.1186/s12929-015-0170-y
https://doi.org/10.1186/s12929-015-0170-...

86. Hayashi D, Kubota R, Takenouchi N , Nakamura T, Umehara F, Arimura K , et al. Accumulation of human T-lymphotropic virus type I (HTLV-I)-infected cells in the cerebrospinal fluid during the exacerbation of HTLV-I-associated myelopathy. J Neurovirol [Internet]. 2008 Oct [cited 2020 Oct 15] ; 14(5):459-63. Available from: https://doi.org/10.1080/13550280802178538
https://doi.org/10.1080/1355028080217853... ^-⁸⁷87. Lezin A, Olindo S, Oliere S, Varrin-Doyer M, Martin R, Cabre P, et al. Human T lymphotropic virus type I (HTLV-I) proviral load in cerebrospinal fluid: a new criterion for the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis? J Infect Dis [Internet]. 2005 Jun [cited 2020 Oct 15] ; 191(11):1830-4. Available from: https://doi.org/10.1086/429962
https://doi.org/10.1086/429962... Sin embargo, se deben evaluar otros marcadores de valor pronóstico, para identificar a las personas con mayor riesgo de la enfermedad.⁸⁸88. Starling ALB, Coelho-dos-Reis JGA, Peruhype-Magalhães V, Pascoal-Xavier MA, Gonçalves DU, Béia SR, et al. Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity. Biomarkers [Internet]. 2015 [cited 2020 Oct 15] ; 20(6-7):502-12. Available from: https://doi.org/10.3109/1354750x.2015.1094141
https://doi.org/10.3109/1354750x.2015.10...

89. Yamauchi J, Araya N, Yagishita N, Sato T, Yamano Y. An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) focusing on clinical and laboratory biomarkers. Pharmacol Ther [Internet]. 2020 Aug [cited 2020 Oct 15] ; 107669. Available from: https://doi.org/10.1016/j.pharmthera.2020.107669
https://doi.org/10.1016/j.pharmthera.202... ^-⁹⁰90. Apoliano CF, Assone T , Maciel da Silva BC, Corral MA, Oliveira ACP , Fonseca LAM , et al. Interferon-γ secretion enzyme-linked immunospot assay determined among human T cell lymphotropic virus type 1-infected subjects: a potential laboratory marker for early HTLV-1-associated myelopathy/tropical spastic paraparesis diagnosis. AIDS Res Hum Retroviruses [Internet]. 2020 Jan [cited 2020 Oct 15] ; 36(1):6-7. Available from: https://doi.org/10.1089/aid.2018.0290
https://doi.org/10.1089/aid.2018.0290...

Leucemia/linfoma de células T del adulto

La neoplasia de células T periféricas causada por HTLV-1 se presenta con leucocitosis, se caracteriza por la presencia de linfocitos anormales (células florales - flower cells) y, clínicamente, por linfadenopatías, lesiones cutáneas, disfunción multiorgánica resultante de la invasión de células neoplásicas, además de la presencia de infecciones oportunistas. Son característicos los niveles elevados de la enzima lactato deshidrogenasa y la hipercalcemia. En Japón, hay más de un millón de portadores y la incidencia de ATLL varía de 0,6 a 0,7 por 1000 personas/año.⁹¹91. Tajima K, Cartier L. Epidemiological features of HTLV-I and adult T cell leukemia. Intervirology [Internet]. 1995 [cited 2020 Oct 15] ; 38(3-4):238-46. Available from: https://doi.org/10.1159/000150438
https://doi.org/10.1159/000150438... El riesgo de enfermedad es mayor en los hombres y los síntomas comienzan 20 a 30 años después. Infección.⁹²92. Kondo T, Kono H, Miyamoto N, Yoshida R, Toki H, Matsumoto I, et al. Age- and sex-specific cumulative rate and risk of ATLL for HTLV-I carriers. Int J cancer [Internet]. 1989 Jun [cited 2020 Oct 15] ; 43(6):1061-4. Available from: https://doi.org/10.1002/ijc.2910430618
https://doi.org/10.1002/ijc.2910430618... Rara vez ocurre ATLL antes de los 30 años; sin embargo, tiende a aumentar hasta los 70 años. También en Japón, donde la probabilidad de desarrollar ATLL es del 5%, los factores de riesgo se consideran (i) transmisión materna, (ii) edad avanzada, (iii) aumento de la carga proviral en sangre periférica, (iv) antecedentes familiares de ATLL y (v) prueba previa positiva para anti-HTLV-1.⁹³93. Nosaka K, Iwanaga M, Imaizumi Y, Ishitsuka K , Ishizawa K, Ishida Y, et al. Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-2011: a nationwide survey. Cancer Sci [Internet]. 2017 Dec [cited 2020 Oct 15] ; 108(12):2478-86. Available from: https://doi.org/10.1111/cas.13398
https://doi.org/10.1111/cas.13398... ^,⁹⁴94. Iwanaga M , Watanabe T, Utsunomiya A , Okayama A , Uchimaru K , Koh KR, et al. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood [Internet]. 2010 Aug [cited 2020 Oct 15] ; 116(8):1211-9. Available from: https://doi.org/10.1182/blood-2009-12-257410
https://doi.org/10.1182/blood-2009-12-25... La ATLL es rara en otros países, no llega al 2% de los casos,⁹⁵95. Phillips AA, Shapira I, Willim RD, Sanmugarajah J, Solomon WB, Horwitz SM, et al. A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma: a multicenter clinicopathologic experience and new prognostic score. Cancer [Internet]. 2010 Jul [cited 2020 Oct 15] ; 116(14):3438-46. Available from: https://doi.org/10.1002/cncr.25147
https://doi.org/10.1002/cncr.25147... a pesar de evidencias de falta de diagnóstico.⁹⁶96. Rosadas C , Puccioni-Sohler M , Oliveira ACP , Casseb J , Sousa M, Taylor GP . Adult T-cell leukaemia/lymphoma in Brazil: a rare disease or rarely diagnosed? Br J Haematol [Internet]. 2020 Feb [cited 2020 Oct 15] ; 188(4):e46-9. Available from: https://doi.org/10.1111/bjh.16318
https://doi.org/10.1111/bjh.16318... ^,⁹⁷97. van Tienen C, Visser O, Lugtenburg P, Taylor G, Cook L. Overrepresentation of patients from HTLV-1 endemic countries among T cell Non-Hodgkin lymphomas in the Netherlands: an indication of under-diagnosis of Adult T cell leukaemia/lymphoma. Br J Haematol [Internet]. 2018 Feb [cited 2020 Oct 15] ; 184(4):688-9. Available from: https://doi.org/10.1111/bjh.15160
https://doi.org/10.1111/bjh.15160...

Son reconocidas cuatro formas clínicas de la ATLL,⁹⁸98. Lymphoma Study Group. Major prognostic factors of patients with adult T-cell leukemia-lymphoma: a cooperative study. Leuk Res [Internet]. 1991 [cited 2020 Oct 15] ; 15(2-3):81-90. Available from: https://doi.org/10.1016/0145-2126(91)90087-A
https://doi.org/10.1016/0145-2126(91)900... que llevan en consideración la presencia y la gravedad de las manifestaciones leucémicas, además de exámenes de laboratorio alterados, como aumento de lactato deshidrogenasa e hipercalcemia. Esa clasificación está descrita en la Figura 1, y los factores que predicen peor pronóstico, incluyendo los arriba mencionados, están en la Figura 2.⁵¹51. Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, et al. Treatment and survival among 1594 patients with ATL. Blood [Internet]. 2015 Dec [cited 2020 Oct 15] ; 126(24):2570-7. Available from: https://doi.org/10.1182/blood-2015-03-632489
https://doi.org/10.1182/blood-2015-03-63... ^,⁹⁸98. Lymphoma Study Group. Major prognostic factors of patients with adult T-cell leukemia-lymphoma: a cooperative study. Leuk Res [Internet]. 1991 [cited 2020 Oct 15] ; 15(2-3):81-90. Available from: https://doi.org/10.1016/0145-2126(91)90087-A
https://doi.org/10.1016/0145-2126(91)900...

99. Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington Jr W, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol [Internet]. 2009 Jan [cited 2020 Oct 15] ; 27(3):453-9. Available from: https://doi.org/10.1200/jco.2008.18.2428
https://doi.org/10.1200/jco.2008.18.2428...

100. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol [Internet]. 1991 Nov [cited 2020 Oct 15] ; 79(3):428-37. Available from: https://doi.org/10.1111/j.1365-2141.1991.tb08051.x
https://doi.org/10.1111/j.1365-2141.1991... ^-¹⁰¹101. Yared JA, Kimball AS. Optimizing management of patients with adult T cell leukemia-lymphoma. Cancers (Basel) [Internet]. 2015 Dec [cited 2020 Oct 15] ; 7(4):2318-29. Available from: https://dx.doi.org/10.3390%2Fcancers7040893
https://doi.org/10.3390%2Fcancers7040893...

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Figura 1
Clasificación y características de la leucemia/linfoma de células T del adulto

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Figura 2
Factores de predicción de peor pronóstico da leucemia/linfoma de células T del adulto

Alteraciones dermatológicas en el individuo con HTLV

Además de las manifestaciones clínicas clásicamente asociadas al HTLV-1, como la dermatitis infecciosa y las manifestaciones cutáneas de ATLL, se han descrito otras condiciones dermatológicas atribuidas a la infección como formas graves de sarna (especialmente en coinfectados con VIH-1), ictiosis, dermatitis seborreica y dermatofitosis.¹⁰³103. Dantas L, Netto E, Glesby MJ, Carvalho EM, Machado P. Dermatological manifestations of individuals infected with human T cell lymphotropic virus type I (HTLV-I). Int J Dermatol [Internet]. 2014 Sep [cited 2020 Oct 15] ; 53(9):1098-102. Available from: https://doi.org/10.1111/ijd.12170
https://doi.org/10.1111/ijd.12170...

Inicialmente, la dermatitis infecciosa se describió en niños jamaicanos infectados por HTLV-1,¹⁰⁴104. LaGrenade L, Hanchard B , Fletcher V, Cranston B, Blattner W. Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet (London, England) [Internet]. 1990 Dec [cited 2020 Oct 15] ; 336(8727):1345-7. Available from: https://doi.org/10.1016/0140-6736(90)92896-p
https://doi.org/10.1016/0140-6736(90)928... principalmente cuando existe transmisión vertical, aunque la enfermedad también puede afectar a adolescentes y adultos.¹⁰⁵105. Bittencourt AL, Primo J, Oliveira MFP. Manifestations of the human T-cell lymphotropic virus type I infection in childhood and adolescence. J Pediatr (Rio J) [Internet]. 2006 [cited 2020 Oct 15] ; 82(6):411-20. Available from: http://dx.doi.org/10.2223/JPED.1573
https://doi.org/10.2223/JPED.1573... La dermatitis infecciosa se caracteriza por lesiones eritematosas que afectan principalmente el cuero cabelludo, regiones retroauriculares, cuello, cara, axilas e inglés. Suele asociarse a infección por bacterias Gram positivas, como Streptococcus beta-hemoliticus y Staphylococcus aureus. Según un estudio de serie de casos, casi la mitad de las personas que tuvieron un seguimiento a largo plazo también fueron diagnosticadas con HAM.¹⁰⁶106. Oliveira MFSP, Fatal PL, Primo JRL, Silva JLS, Batista ES, Ferré L, et al. Infective dermatitis associated with human T-cell lymphotropic virus type 1: evaluation of 42 cases observed in Bahia, Brazil. Clin Infect Dis [Internet]. 2012 Jun [cited 2020 Oct 15] ; 54(12):1714-9. Available from: https://doi.org/10.1093/cid/cis273
https://doi.org/10.1093/cid/cis273... El diagnóstico diferencial incluye otras causas de eczema crónico, como la dermatitis atópica y la dermatitis seborreica.¹⁰⁶106. Oliveira MFSP, Fatal PL, Primo JRL, Silva JLS, Batista ES, Ferré L, et al. Infective dermatitis associated with human T-cell lymphotropic virus type 1: evaluation of 42 cases observed in Bahia, Brazil. Clin Infect Dis [Internet]. 2012 Jun [cited 2020 Oct 15] ; 54(12):1714-9. Available from: https://doi.org/10.1093/cid/cis273
https://doi.org/10.1093/cid/cis273... La presencia de lesiones características, rinorrea crónica, dermatitis crónica recurrente y serología positiva para HTLV son los principales criterios para el diagnóstico de dermatitis infecciosa, cuyo tratamiento consiste en la administración de antibióticos asociados al uso tópico de corticosteroides, combinados o no con antifúngicos.

Las alteraciones dermatológicas en ATLL son bastante variadas (eritrodermia, pápulas, nódulos, lesiones infiltrantes o placas eritematosas) y dependen del estadio de la enfermedad; los nódulos son más frecuentes en las formas graves, especialmente en la forma aguda linfomatosa, o primaria cutánea tumoral.¹⁰⁷107. Bittencourt AL, Oliveira MFP. Cutaneous manifestations associated with HTLV-1 infection. Int J Dermatol [Internet]. 2010 Oct [cited 2020 Oct 15] ; 49(10):1099-110. Available from: https://doi.org/10.1111/j.1365-4632.2010.04568.x
https://doi.org/10.1111/j.1365-4632.2010... Las lesiones pueden tener una evolución indolente y cambiar con la utilización de corticoides. La evaluación histopatológica es fundamental para el diagnóstico específico.

Uveítis en el individuo con HTLV-1

En Japón, la uveítis se informó por primera vez en 1989.¹⁰⁸108. Ohba N, Matsumoto M, Sameshima M, Kabayama Y, Nakao K, Unoki K, et al. Ocular manifestations in patients infected with human T-lymphotropic virus type I. Jpn J Ophthalmol. 1989;33(1):1-12. Más común en personas de hasta 50 años y un poco más frecuente en mujeres, su incidencia exacta entre los portadores de HTLV-1 sigue siendo incierta. La enfermedad se manifiesta por alteraciones visuales, que incluyen 'moscas volantes' y visión borrosa o nublada; y es bilateral en casi la mitad de las personas afectadas.¹⁰⁹109. Mochizuki M, Tajima K, Watanabe T , Yamaguchi K. Human T lymphotropic virus type 1 uveitis. Br J Ophthalmol [Internet]. 1994 Feb [cited 2020 Oct 15] ; 78(2):149-54. Available from: https://dx.doi.org/10.1136%2Fbjo.78.2.149
https://doi.org/10.1136%2Fbjo.78.2.149... Los signos oculares incluyen: iritis; opacidades vítreas; vasculitis retiniana; y hemorragias y exudados retinianos. Hay una buena respuesta del paciente a los corticosteroides tópicos o sistémicos, aunque la recidiva es común con la interrupción del tratamiento.

Coinfecciones en el individuo con HTLV

El individuo infectado por HTLV puede tener algunas coinfecciones, con mayor frecuencia que la población en general, ya sea por compartir vías de infección o como resultado de las alteraciones inmunológicas inducidas por la propia infección. Además, el HTLV puede alterar la historia natural de algunas infecciones en situaciones de coinfección.

En la coinfección por VIH, por ejemplo, la evidencia sugiere un papel neutral o incluso protector para los coinfectados con HTLV-2.¹¹⁰110. Brites C, Sampalo J, Oliveira A. HIV/human T-cell lymphotropic virus coinfection revisited: impact on AIDS progression. AIDS Rev [Internet]. 2009 Jan-Mar [cited 2020 Oct 15] ; 11(1):8-16. Available from: https://pubmed.ncbi.nlm.nih.gov/19290030 /
https://pubmed.ncbi.nlm.nih.gov/19290030... Sin embargo, si esta coinfección es causada por HTLV-1, los datos existentes muestran un mayor riesgo de muerte, tanto en adultos como en niños coinfectados.¹¹¹111. Pedroso C, Netto EM, Weyll N, Brites C. Coinfection by HIV-1 and human lymphotropic virus type 1 in Brazilian children is strongly associated with a shorter survival time. J Acquir Immune Defic Syndr [Internet]. 2011 Aug [cited 2020 Oct 15] ; 57 Suppl 3:S208-11. Available from: https://doi.org/10.1097/qai.0b013e31821e9baf
https://doi.org/10.1097/qai.0b013e31821e... Los motivos de estos hallazgos no son muy claros, siendo una hipótesis de explicación el retraso en la introducción de la terapia antirretroviral, debido al aumento del conteo de células T-CD4+ provocado por el HTLV-1, sin beneficios clínicos. Los individuos coinfectados, tratados con antirretrovirales y con la viremia del VIH suprimida, tienen una supervivencia similar a la de los pacientes monoinfectados en las mismas condiciones; pero, en aquellos con carga viral detectable, la supervivencia es significativamente menor para los coinfectados.¹¹²112. Brites C, Miranda F, Luz E, Netto EM. Early and successful combination antiretroviral therapy normalizes survival time in patients coinfected with human immunodeficiency virus and human T-cell lymphotrophic virus type 1. Clin Infect Dis [Internet]. 2020 Jun [cited 2020 Oct 15] ; 71(1):196-200. Available from: https://doi.org/10.1093/cid/ciz756
https://doi.org/10.1093/cid/ciz756...

En cuanto a la coinfección por el virus de la hepatitis C, los datos existentes son contradictorios: mientras que algunos estudios muestran un aumento de la viremia del virus de la hepatitis C y una menor probabilidad de eliminación espontánea de la infección,¹¹³113. Boschi-Pinto C, Stuver S, Okayama A , Trichopoulod D, Orav EJ, Tsubouchi H, et al. A followu-p study of morbidity and mortality associated with hepatitis C virus infection and its interaction with human T lymphotropic virus type I in Miyazaki, Japan. J Infect Dis [Internet]. 2000 Jan [cited 2020 Oct 15] ; 181(1):35-41. Available from: https://doi.org/10.1086/315177
https://doi.org/10.1086/315177... otros sugieren una mayor probabilidad de eliminar este virus en personas infectadas y HTLV, probablemente debido a la inmunomodulación causada por HTLV en este grupo de individuos, resultado de la alta producción de citocinas proinflamatorias.¹¹⁴114. Brites C, Abrahão M, Bozza P, Netto EM, Lyra A, Bahia F. Infection by HTLV-1 Is associated with high levels of proinflammatory cytokines in HIV-HCV-coinfected patients. J Acquir Immune Defic Syndr [Internet]. 2018 Feb [cited 2020 Oct 15] ; 77(2):230-4. Available from: https://doi.org/10.1097/qai.0000000000001576
https://doi.org/10.1097/qai.000000000000... Además, existen estudios que sugieren menor daño hepático en individuos triplemente infectados - con VIH, HTLV y el virus de la hepatitis C - y una mayor probabilidad de eliminación espontánea del virus de la hepatitis C.¹¹⁵115. Bahia F, Novais V, Evans J, Marchand CL, Netto E, Page K, et al. The impact of human T-cell lymphotropic virus i infection on clinical and immunologic outcomes in patients coinfected with HIV and hepatitis C virus. J Acquir Immune Defic Syndr [Internet]. 2011 Aug [cited 2020 Oct 15] ; 57(3):S202-7. Available from: https://dx.doi.org/10.1097%2FQAI.0b013e31821e9a1e
https://doi.org/10.1097%2FQAI.0b013e3182... ^,¹¹⁶116. Marchand CL, Bahia F, Page K, Brites C. Hepatitis C virus infection and spontaneous clearance in HTLV-1 and HIV co-infected patients in Salvador, Bahia, Brazil. Braz J Infect Dis [Internet]. 2015 [cited 2020 Oct 15] ; 19(5):486-91. Available from: http://dx.doi.org/10.1016/j.bjid.2015.06.007
https://doi.org/10.1016/j.bjid.2015.06.0... Individuos portadores de coinfección HTLV-1 y Strongyloides stercoralis sufren un impacto negativo en el curso de ambas infecciones, tornándose más susceptibles a formas más graves de estrongiloidiasis, resistencia terapéutica, además de presentar una carga proviral del HTLV-1 superior y mayor riesgo de transmisión vertical del HTLV.¹¹⁷117. Gillet NA, Cook L , Laydon DJ , Hlela C, Verdonck K, Alvarez C, et al. Strongyloidiasis and infective dermatitis alter human T lymphotropic virus-1 clonality in vivo. PLoS Pathog [Internet]. 2013 Apr [cited 2020 Oct 15] ; 9(4):e1003263. Available from: https://dx.doi.org/10.1371%2Fjournal.ppat.1003263
https://doi.org/10.1371%2Fjournal.ppat.1...

118. Nakada K, Yamaguchi K , Furugen S, Nakasone K, Oshiro Y, Kohakura M, et al. Monoclonal integration of HTLV-I proviral DNA in patients with strongyloidiasis. Int J Cancer [Internet]. 1987 Aug [cited 2020 Oct 15] ; 40(2):145-8. Available from: https://doi.org/10.1002/ijc.2910400203
https://doi.org/10.1002/ijc.2910400203...

119. Newton RC, Limpuangthip P, Greenberg S, Gam A, Neva FA. Strongyloides stercoralis hyperinfection in a carrier of HTLV-I virus with evidence of selective immunosuppression. Am J Med [Internet]. 1992 Feb [cited 2020 Oct 15] ; 92(2):202-8. Available from: https://doi.org/10.1016/0002-9343(92)90113-p
https://doi.org/10.1016/0002-9343(92)901...

120. Terashima A, Alvarez H, Tello R, Infante R, Freedman DO, Gotuzzo E. Treatment failure in intestinal strongyloidiasis: an indicator of HTLV-I infection. Int J Infect Dis [Internet]. 2002 Mar [cited 2020 Oct 15] ; 6(1):28-30. Available from: https://doi.org/10.1016/s1201-9712(02)90132-3
https://doi.org/10.1016/s1201-9712(02)90...

121. Gotuzzo E, Moody J, Verdonck K , Cabada MM, González E, van Dooren S, et al. Frequent HTLV-1 infection in the offspring of Peruvian women with HTLV-1 - associated myelopathy / tropical spastic paraparesis or strongyloidiasis. Rev Panam Salud Publica [Internet]. 2007 Oct [cited 2020 Oct 15] ; 22(4):223-30. Available from: https://doi.org/10.1590/s1020-49892007000900001
https://doi.org/10.1590/s1020-4989200700...

122. Porto MAF, Muniz A , Oliveira Jr J, Carvalho EM. Implicações clinicas e imunológicas da associação entre o HTLV-1 e a estrongiloidíase. Rev Soc Bras Med Trop [Internet]. 2002 [citado 2020 out 15]; 35(6):641-9. Disponível em: https://doi.org/10.1590/S0037-86822002000600016
https://doi.org/10.1590/S0037-8682200200...

123. Sato Y, Shiroma Y. Concurrent infections with Strongyloides and T-cell leukemia virus and their possible effect on immune responses of host. Clin Immunol Immunopathol [Internet]. 1989 Aug [cited 2020 Oct 15] ; 52(2):214-24. Available from: https://doi.org/10.1016/0090-1229(89)90173-6
https://doi.org/10.1016/0090-1229(89)901...

124. Salles F, Bacellar A, Amorim M, Orge G, Sundberg M, Lima M, et al. Treatment of strongyloidiasis in HTLV-1 and Strongyloides stercoralis coinfected patients is associated with increased tnfα and decreased soluble IL2 receptor levels. Trans R Soc Trop Med Hyg [Internet]. 2013 Aug [cited 2020 Oct 15] ; 107(8):526-9. Available from: https://doi.org/10.1093/trstmh/trt052
https://doi.org/10.1093/trstmh/trt052...

125. Gabet A-S, Mortreux F, Talarmin A, Plumelle Y, Leclercq I, Leroy A, et al. High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis. Oncogene [Internet]. 2000 Oct [cited 2020 Oct 15] ; 19(43):4954-60. Available from: https://doi.org/10.1038/sj.onc.1203870
https://doi.org/10.1038/sj.onc.1203870... ^-¹²⁶126. Plumelle Y, Gonin C, Edouard A, Bucher BJ, Thomas L, Brebion A, et al. Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia. Am J Clin Pathol [Internet]. 1997 Jan [cited 2020 Oct 15] ; 107(1):81-7. Available from: https://doi.org/10.1093/ajcp/107.1.81
https://doi.org/10.1093/ajcp/107.1.81...

Individuos con HTLV-1 tienen más riesgo de infección por Mycobacterium tuberculosis,¹²⁷127. Schierhout G , McGregor S , Gessain A , Einsiedel L , Martinello M , Kaldor J . Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis [Internet]. 2019 Apr [cited 2020 Oct 15] ; 20(4):407-8. Available from: https://doi.org/10.1016/S1473-3099(20)30133-X
https://doi.org/10.1016/S1473-3099(20)30...

128. Marinho J, Galvao-Castro B, Rodrigues LC, Barreto ML . Increased risk of tuberculosis with human T-lymphotropic virus-1 infection a case-control study. J Acquir Immune Defic Syndr [Internet]. 2005 [cited 2020 Oct 15] ; 40(5):625-8. Available from: https://www.arca.fiocruz.br/handle/icict/8131
https://www.arca.fiocruz.br/handle/icict...

129. Norrgren HR, Bamba S, Larsen O, Silva Z, Aaby P, Koivula T, et al. Increased prevalence of HTLV-1 in patients with pulmonary tuberculosis coinfected with HIV, but not in HIV-negative patients with tuberculosis. J Acquir Immune Defic Syndr [Internet]. 2008 Aug [cited 2020 Oct 15] ; 48(5):607-10. Available from: https://doi.org/10.1097/qai.0b013e31817efb83
https://doi.org/10.1097/qai.0b013e31817e...

130. Moreira ED, Ribeiro TT, Swanson P, Sampoio Filho C, Melo A, Brites C, et al. Seroepidemiology of human T-cell lymphotropic virus type I/II in northeastern Brazil. J Acquir Immune Defic Syndr . 1993 Aug;6(8):959-63.

131. Hanada S , Uematsu T, Iwahashi M, Nomura K, Utsunomiya A , Kodama M, et al. The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan. Cancer [Internet]. 1989 Sep [cited 2020 Oct 15] ; 64(6):1290-5. Available from: https://doi.org/10.1002/1097-0142(19890915)64:6%3C1290::aid-cncr2820640620%3E3.0.co;2-z
https://doi.org/10.1002/1097-0142(198909... ^-¹³²132. Verdonck K , Gonzalez E, Schrooten W, Vanham G, Gotuzzo E . HTLV-1 infection is associated with a history of active tuberculosis among family members of HTLV-1-infected patients in Peru. Epidemiol Infect [Internet]. 2008 Aug [cited 2020 Oct 15] ; 136(8):1076-83. Available from: https://dx.doi.org/10.1017%2FS0950268807009521
https://doi.org/10.1017%2FS0950268807009... siendo que el impacto clínico de esa coinfección, aún es carente de esclarecimiento.

Diagnóstico

En Brasil, las pruebas de rutina para HTLV-1/2 en donantes de sangre y órganos se vienen realizando desde 1993 y 2009, respectivamente.⁴²42. Brasil. Ministério da Saúde. Portaria GM/MS n. 1376, de 19 de novembro de 1993. Aprova alterações na Portaria no 721/GM, de 09.08.89, que aprova Normas Técnicas para coleta, processamento e transfusão de sangue, componentes e derivados, e dá outras providências [Internet]. Diário Oficial da União , Brasília (DF), 1993 dez 2 [citado 2020 out 15]; Seção I:18405. Disponível em: http://redsang.ial.sp.gov.br/site/docs_leis/ps/ps29.pdf
http://redsang.ial.sp.gov.br/site/docs_l... ^,¹³³133. Brasil. Ministério da Saúde. Portaria n. 2.600, de 21 de outubro de 2009. Aprova o Regulamento Técnico do Sistema Nacional de Transplantes [Internet]. Diário Oficial da União , Brasília (DF), 2009 out 30 [citado 2020 jun 14]; Seção I:77. Disponível em:http://bvsms.saude.gov.br/bvs/saudelegis/gm/2009/prt2600_21_10_2009.html
http://bvsms.saude.gov.br/bvs/saudelegis... En ambos casos, la infección es un criterio de exclusión del donante. En Brasil, aunque no existe una política nacional de detección del HTLV-1/2 en la atención prenatal, la prueba se realiza de forma rutinaria en algunos estados del país. La Ordenanza MS SCTIE nº 23, de 31 de mayo de 2016, incluyó la prueba de western blot y la reacción en cadena de la polimerasa (polymerase chain reaction, PCR) para la confirmación de la infección por HTLV-1 en personas con sospecha de ATLL tratadas por el Sistema Único de Salud (SUS).¹³⁴134. Brasil. Ministério da Saúde. Portaria n. 23, de 31 de maio de 2016. Torna pública a decisão de incorporar os procedimentos laboratoriais por técnicas de Western Blot e PCR em tempo real no diagnóstico de leucemia/linfoma de células T do adulto associado ao HTLV-1, no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União , Brasília (DF), 2016 jun 6 [citado 2020 jun 14]; Seção I:45. Disponível em:http://bvsms.saude.gov.br/bvs/saudelegis/sctie/2016/prt0023_31_05_2016.html%09%09%09%09%09%09
http://bvsms.saude.gov.br/bvs/saudelegis... La Figura 3 muestra las indicaciones para las pruebas de HTLV-1/2. El diagnóstico de laboratorio de la infección debe realizarse mediante pruebas de cribado, seguidas de pruebas de confirmación en una muestra de sangre diferente cuando el resultado de la prueba de cribado sea positivo¹³⁵135. Itabashi K, Miyazawa T, Sekizawa A, Tokita A, Saito S, Moriuchi H, et al. A nationwide antenatal human T-cell leukemia virus type-1 antibody screening in Japan. Front Microbiol [Internet]. 2020 Apr [cited 2020 Oct 15] ; 11:595. Available from: https://dx.doi.org/10.3389%2Ffmicb.2020.00595
https://doi.org/10.3389%2Ffmicb.2020.005...

136. Cassar O , Gessain A . Serological and molecular methods to study epidemiological aspects of human T-cell lymphotropic virus type 1 infection. Methods Mol Biol [Internet]. 2017 [cited 2020 Oct 15] ; 1582:3-24. Available from: https://doi.org/10.1007/978-1-4939-6872-5_1
https://doi.org/10.1007/978-1-4939-6872-... ^-¹³⁷137. Puccioni-Sohler M , Grassi MFR , Galvão-Castro B, Caterino A, Proietti ABFC, Vicente ACP , et al. Increasing awareness of human T-lymphotropic virus type-1 infection: a serious, invisible, and neglected health problem in Brazil. Rev Soc Bras Med Trop [Internet]. 2019 Oct [cited 2020 Oct 15] ; 52:e20190343. Available from: http://dx.doi.org/10.1590/0037-8682-0343-2019
https://doi.org/10.1590/0037-8682-0343-2... (Figura 4).

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Figura 3
Indicaciones de pruebas de laboratorio para el virus linfotrópico de células T humanas (HTLV-1/2)

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Figura 4
Recomendaciones para el diagnóstico de laboratorio de la infección por el virus linfotrópico de células T humanas (HTLV-1/2)

Las pruebas de cribado se utilizan para detectar anticuerpos contra HTLV-1/2 en plasma o suero. Las técnicas de laboratorio para realizar estas pruebas incluyen (i) reacción inmunoenzimática, (ii) quimioluminiscencia y (iii) aglutinación de partículas.¹³⁶136. Cassar O , Gessain A . Serological and molecular methods to study epidemiological aspects of human T-cell lymphotropic virus type 1 infection. Methods Mol Biol [Internet]. 2017 [cited 2020 Oct 15] ; 1582:3-24. Available from: https://doi.org/10.1007/978-1-4939-6872-5_1
https://doi.org/10.1007/978-1-4939-6872-... Las pruebas de detección son muy sensibles y el resultado negativo excluye la infección, a menos que haya evidencia de exposición reciente al virus, cuando se recomienda repetir el examen a los 90 días.²⁴24. Cook LBM, Melamed A, Demontis MA, Laydon DJ, Fox JM, Tosswill JHC, et al. Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients. Retrovirology [Internet]. 2016 Jan [cited 2020 Oct 15] ; 13:3. Available from: https://doi.org/10.1186/s12977-015-0236-7
https://doi.org/10.1186/s12977-015-0236-... ^,²⁵25. Manns A, Wilks RJ, Murphy EL, Haynes G, Barnett M, Hanchard B, et al. A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion. Int J Cancer [Internet]. 1992 Jul [cited 2020 Oct 15] ; 51(6):886-91. Available from: https://doi.org/10.1002/ijc.2910510609
https://doi.org/10.1002/ijc.2910510609... La especificidad de las pruebas de detección en Brasil varía del 92 al 99,5%. Se recomiendan las pruebas de confirmación para excluir resultados falsos positivos en una prueba de detección.¹³⁶136. Cassar O , Gessain A . Serological and molecular methods to study epidemiological aspects of human T-cell lymphotropic virus type 1 infection. Methods Mol Biol [Internet]. 2017 [cited 2020 Oct 15] ; 1582:3-24. Available from: https://doi.org/10.1007/978-1-4939-6872-5_1
https://doi.org/10.1007/978-1-4939-6872-...

137. Puccioni-Sohler M , Grassi MFR , Galvão-Castro B, Caterino A, Proietti ABFC, Vicente ACP , et al. Increasing awareness of human T-lymphotropic virus type-1 infection: a serious, invisible, and neglected health problem in Brazil. Rev Soc Bras Med Trop [Internet]. 2019 Oct [cited 2020 Oct 15] ; 52:e20190343. Available from: http://dx.doi.org/10.1590/0037-8682-0343-2019
https://doi.org/10.1590/0037-8682-0343-2... ^-¹³⁸138. Silva Brito V, Santos FLN, Gonçalves NLS, Araújo THA, Nascimento DSV, Pereira FM, et al. Performance of commercially available serological screening tests for human T-cell lymphotropic virus infection in Brazil. J Clin Microbiol [Internet]. 2018 Nov [cited 2020 Oct 15] ; 56(12):e00961. Available from: https://doi.org/10.1128/jcm.00961-18
https://doi.org/10.1128/jcm.00961-18...

Las pruebas de confirmación identifican anticuerpos contra diferentes antígenos HTLV-1 y HTLV-2, o amplifican e identifican material genético proviral, generalmente en linfocitos de sangre periférica. Las pruebas confirmatorias y de tipificación viral son (i) western blot, (ii) inmunoensayo en línea (LIA) y (iii) PCR.¹³⁶136. Cassar O , Gessain A . Serological and molecular methods to study epidemiological aspects of human T-cell lymphotropic virus type 1 infection. Methods Mol Biol [Internet]. 2017 [cited 2020 Oct 15] ; 1582:3-24. Available from: https://doi.org/10.1007/978-1-4939-6872-5_1
https://doi.org/10.1007/978-1-4939-6872-...

Habitualmente, el western blot y el LIA suelen ser suficientes para el diagnóstico; sin embargo, en algunos casos, puede ocurrir un resultado indeterminado o incertidumbre con respecto al tipo de HTLV,¹³⁹139. Cánepa C, Salido J, Ruggieri M, Fraile S, Pataccini G, Berinii C, et al. Low Proviral load is associated with indeterminate western blot patterns in human T-cell lymphotropic virus type 1 infected individuals: could punctual mutations be related? Viruses [Internet]. 2015 Nov [cited 2020 Oct 15] ; 7(11):5643-58. Available from: https://dx.doi.org/10.3390%2Fv7112897
https://doi.org/10.3390%2Fv7112897...

140. Tebourski F, Slim A, Elgaaied A. The significance of combining World Health Organization and Center for Disease Control criteria to resolve indeterminate human immunodeficiency virus type-1 Western blot results. Diagn Microbiol Infect Dis [Internet]. 2004 Jan [cited 2020 Oct 15] ; 48(1):59-61. Available from: https://doi.org/10.1016/j.diagmicrobio.2003.08.004
https://doi.org/10.1016/j.diagmicrobio.2...

141. Ishak R , Vallinoto ACR , Azevedo VN , Vicente ACP , Hall WW , Ishak MO Molecular evidence for infection by HTLV-2 among individuals with negative serological screening tests for HTLV antibodies. Epidemiol Infect [Internet]. 2007 May [cited 2020 Oct 15] ; 135(4):604-9. Available from: https://doi.org/10.1017/s0950268806006984
https://doi.org/10.1017/s095026880600698...

142. Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T , Umeki K, et al. Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. J Clin Microbiol [Internet]. 2017 Sep [cited 2020 Oct 15] ; 55(9):2838-49. Available from: https://doi.org/10.1128/jcm.00659-17
https://doi.org/10.1128/jcm.00659-17...

143. Araujo A C , Casseb J S , Neitzert E, Souza ML, Mammano F, Mistro AD, et al. HTLV-I and HTLV-II infections among HIV-1 seropositive patients in Sao Paulo, Brazil. Eur J Epidemiol [Internet]. 1994 Apr [cited 2020 Oct 15] ; 10(2):165-71. Available from: https://doi.org/10.1007/bf01730366
https://doi.org/10.1007/bf01730366...

144. Campos KR, Gonçalves MG, Costa NA, Caterino-de-Araujo A . Comparative performances of serologic and molecular assays for detecting human T lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) in patients infected with human immunodeficiency virus type 1 (HIV-1). Brazilian J Infect Dis [Internet]. 2017 [cited 2020 Oct 15] ; 21(3):297-305. Available from: http://dx.doi.org/10.1016/j.bjid.2017.02.005
https://doi.org/10.1016/j.bjid.2017.02.0...

145. Jacob F, Santos-Fortuna E, Azevedo RS, Caterino-de-Araujo A . Serological patterns and temporal trends of HTLV-1/2 infection in high-risk populations attending Public Health Units in São Paulo, Brazil. J Clin Virol [Internet]. 2008 Jun [cited 2020 Oct 15] ; 42(2):149-55. Available from: https://doi.org/10.1016/j.jcv.2008.01.017
https://doi.org/10.1016/j.jcv.2008.01.01...

146. Morimoto HK, Morimoto AA, Reiche EMV, Ueda LT, Matsuo T, Reiche FV, et al. Difficulties in the diagnosis of HTLV-2 infection in HIV/AIDS patients from Brazil: comparative performances of serologic and molecular assays, and detection of HTLV-2b subtype. Rev Inst Med Trop São Paulo [Internet]. 2007 Jul-Aug [cited 2020 Oct 15] ; 49(4):225-30. Available from: http://dx.doi.org/10.1590/S0036-46652007000400006
https://doi.org/10.1590/S0036-4665200700...

147. Mangano AM, Remesar M, del Pozo A, Sen L. Human T lymphotropic virus types I and II proviral sequences in Argentinian blood donors with indeterminate Western blot patterns. J Med Virol [Internet]. 2004 Oct 74(2):323-7. Available from: https://doi.org/10.1002/jmv.20172
https://doi.org/10.1002/jmv.20172...

148. Martins ML, Santos ACS, Namen-Lopes MS, Barbosa-Stancioli EF, Utsch DG, Carneiro-Proietti ABF . Long-term serological follow-up of blood donors with an HTLV-Indeterminate Western Blot: Antibody Profile of Seroconverters and Individuals With False Reactions. J Med Virol [Internet]. 2010 Oct [cited 2020 Oct 15] ; 82(10):1746-53. Available from: https://doi.org/10.1002/jmv.21881
https://doi.org/10.1002/jmv.21881... ^-¹⁴⁹149. Abrams A, Akahata Y, Jacobson S. The prevalence and significance of HTLV-I/II seroindeterminate western blot patterns. Viruses [Internet]. 2011 Aug [cited 2020 Oct 15] ; 3(8):1320-31. Available from: https://dx.doi.org/10.3390%2Fv3081320
https://doi.org/10.3390%2Fv3081320... con mayor frecuencia en individuos infectados con HTLV-2 o VIH-1 o ambos.¹⁴¹141. Ishak R , Vallinoto ACR , Azevedo VN , Vicente ACP , Hall WW , Ishak MO Molecular evidence for infection by HTLV-2 among individuals with negative serological screening tests for HTLV antibodies. Epidemiol Infect [Internet]. 2007 May [cited 2020 Oct 15] ; 135(4):604-9. Available from: https://doi.org/10.1017/s0950268806006984
https://doi.org/10.1017/s095026880600698... ^,¹⁵⁰150. Campos KR , Santos FLN, Silva Brito V, Gonçalves NLS, Araújo THA, Galvão-Castro B , et al. Line immunoassay for confirmation and discrimination of human T-cell lymphotropic virus infections in inconclusive western blot serum samples from Brazil. J Clin Microbiol [Internet]. 2019 Dec [cited 2020 Oct 15] ; 58(1):e01384-19. Available from: https://doi.org/10.1128/jcm.01384-19
https://doi.org/10.1128/jcm.01384-19... El LIA es más preciso para confirmar la infección por HTLV-1 y HTLV-2,¹⁵⁰150. Campos KR , Santos FLN, Silva Brito V, Gonçalves NLS, Araújo THA, Galvão-Castro B , et al. Line immunoassay for confirmation and discrimination of human T-cell lymphotropic virus infections in inconclusive western blot serum samples from Brazil. J Clin Microbiol [Internet]. 2019 Dec [cited 2020 Oct 15] ; 58(1):e01384-19. Available from: https://doi.org/10.1128/jcm.01384-19
https://doi.org/10.1128/jcm.01384-19... ^,¹⁵¹151. Umeki K , Umekita K, Hashikura Y, Yamamoto I, Kubo K, Nagatomo Y, et al. Evaluation of line immunoassay to detect HTLV-1 infection in an endemic area, southwestern Japan; comparison with polymerase chain reaction and western blot. Clin Lab [Internet]. 2017 Feb [cited 2020 Oct 15] ; 63(2):227-33. Available from: https://doi.org/10.7754/clin.lab.2016.160501
https://doi.org/10.7754/clin.lab.2016.16... en comparación con el western blot.¹⁵⁰150. Campos KR , Santos FLN, Silva Brito V, Gonçalves NLS, Araújo THA, Galvão-Castro B , et al. Line immunoassay for confirmation and discrimination of human T-cell lymphotropic virus infections in inconclusive western blot serum samples from Brazil. J Clin Microbiol [Internet]. 2019 Dec [cited 2020 Oct 15] ; 58(1):e01384-19. Available from: https://doi.org/10.1128/jcm.01384-19
https://doi.org/10.1128/jcm.01384-19... ^,¹⁵²152. Okuma K, Kuramitsu M , Niwa T, Taniguchi T, Masaki Y, Ueda G, et al. Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan. Retrovirology [Internet]. 2020 Aug [cited 2020 Oct 15] ; 17(1):26. Available from: https://doi.org/10.1186/s12977-020-00534-0
https://doi.org/10.1186/s12977-020-00534... Los resultados no determinados o no tipados por Western blot o LIA deben enviarse a PCR cualitativa o cuantitativa: se utilizan PCR anidada (nPCR) y PCR en tiempo real (quantitative PCR, qPCR). La RT-PCR permite no solo la cuantificación de la carga proviral de HTLV-1/2, sino también la estratificación del riesgo de que el individuo desarrolle enfermedades asociadas con HTLV-1.²⁶26. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J Neurovirol [Internet]. 1998 Dec [cited 2020 Oct 15] ; 4(6):586-93. Available from: https://doi.org/10.3109/13550289809114225
https://doi.org/10.3109/1355028980911422... ^,⁹³93. Nosaka K, Iwanaga M, Imaizumi Y, Ishitsuka K , Ishizawa K, Ishida Y, et al. Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-2011: a nationwide survey. Cancer Sci [Internet]. 2017 Dec [cited 2020 Oct 15] ; 108(12):2478-86. Available from: https://doi.org/10.1111/cas.13398
https://doi.org/10.1111/cas.13398... ^,⁹⁴94. Iwanaga M , Watanabe T, Utsunomiya A , Okayama A , Uchimaru K , Koh KR, et al. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood [Internet]. 2010 Aug [cited 2020 Oct 15] ; 116(8):1211-9. Available from: https://doi.org/10.1182/blood-2009-12-257410
https://doi.org/10.1182/blood-2009-12-25... ^,¹⁴²142. Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T , Umeki K, et al. Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. J Clin Microbiol [Internet]. 2017 Sep [cited 2020 Oct 15] ; 55(9):2838-49. Available from: https://doi.org/10.1128/jcm.00659-17
https://doi.org/10.1128/jcm.00659-17... ^,¹⁵³153. Primo J, Siqueira I, Nascimento MCF, Oliveira MF, Farre L, Carvalho EM , et al. High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1. Brazilian J Med Biol Res [Internet]. 2009 Jul [cited 2020 Oct 15] ; 42(8):761-4. Available from: https://doi.org/10.1590/S0100-879X2009005000008
https://doi.org/10.1590/S0100-879X200900...

154. Hisada M, Okayama A , Shioiri S, Spiegelman DL, Stuver SO, Mueller NE. Risk factors for adult T-cell leukemia among carriers of human T-lymphotropic virus type I. Blood. 1998 Nov;92(10):3557-61.^-¹⁵⁵155. Rosadas C , Cabral-Castro MJ , Vicente ACP , Peralta JM , Puccioni-Sohler M . Validation of a quantitative real-time PCR assay for HTLV-1 proviral load in peripheral blood mononuclear cells. J Virol Methods [Internet]. 2013 Nov [cited 2020 Oct 15] ; 193(2):536-41. Available from: https://doi.org/10.1016/j.jviromet.2013.07.040
https://doi.org/10.1016/j.jviromet.2013.... La detección de ARN viral no es utilizado en la rutina clínica, ya que la viremia es baja o nula, incluso en individuos con HAM.¹⁵⁶156. Cabral F, Arruda LB, Araújo ML, Montanheiro P, Smid J , Oliveira ACP , et al. Detection of human T-cell lymphotropic virus type 1 in plasma samples. Virus Res [Internet]. 2012 Jan [cited 2020 Oct 15] ; 163(1):87-90. Available from: https://doi.org/10.1016/j.virusres.2011.08.014
https://doi.org/10.1016/j.virusres.2011.... ^,¹⁵⁷157. Demontis MA , Sadiq MT, Golz S, Taylor GP . HTLV-1 viral RNA is detected rarely in plasma of HTLV-1 infected subjects. J Med Virol [Internet]. 2015 Dec [cited 2020 Oct 15] ; 87(12):2130-4. Available from: https://doi.org/10.1002/jmv.24264
https://doi.org/10.1002/jmv.24264...

Hasta el momento de esta publicación, no se encuentra disponible comercialmente una prueba molecular para HTLV-1/2. Las pruebas utilizadas son artesanales, requiriendo validación previa.¹⁵⁵155. Rosadas C , Cabral-Castro MJ , Vicente ACP , Peralta JM , Puccioni-Sohler M . Validation of a quantitative real-time PCR assay for HTLV-1 proviral load in peripheral blood mononuclear cells. J Virol Methods [Internet]. 2013 Nov [cited 2020 Oct 15] ; 193(2):536-41. Available from: https://doi.org/10.1016/j.jviromet.2013.07.040
https://doi.org/10.1016/j.jviromet.2013.... ^,¹⁵⁸158. Tamegão-lopes BP, Rezende PR, Cunha LM. Carga proviral do HTLV-1 e HTLV-2: um método simples através da PCR quantitativa em tempo real. Rev Soc Bras Med Trop [Internet]. 2006 nov-dez [citado 2020 out 15]; 39(6):548-52. Disponível em: https://doi.org/10.1590/S0037-86822006000600007
https://doi.org/10.1590/S0037-8682200600...

159. Medeiros ACM, Vidal LRR, Von Linsingen R, Ferin AN, Strapasson TB, Almeida SM, et al. Confirmatory molecular method for HTLV-1/2 infection in high-risk pregnant women. J Med Virol [Internet]. 2018 May [cited 2020 Oct 15] ; 90(5):998-1001. Available from: https://doi.org/10.1002/jmv.25014
https://doi.org/10.1002/jmv.25014...

160. Kamihira S, Yamano Y , Iwanaga M , Sasaki D, Satake M, Okayama A , et al. Intra- and inter-laboratory variability in human T-cell leukemia virus type-1 proviral load quantification using real-time polymerase chain reaction assays: a multi-center study. Cancer Sci [Internet]. 2010 Nov [cited 2020 Oct 15] ; 101(11):2361-7. Available from: https://doi.org/10.1111/j.1349-7006.2010.01720.x
https://doi.org/10.1111/j.1349-7006.2010... ^-¹⁶¹161. Hayden RT, Gu Z, Ingersoll J, Abdul-Ali D, Pounds S, Caliendo AM, et al. Comparison of droplet digital PCR to real-time PCR for quantitative detection of cytomegalovirus. J Clin Microbiol [Internet]. 2013 Feb [cited 2020 Oct 15] ; 51(2):540-6. Available from: https://doi.org/10.1128/jcm.02620-12
https://doi.org/10.1128/jcm.02620-12... La ausencia de pruebas comerciales y la estandarización de los protocolos nacionales dificulta la implementación de pruebas moleculares en la rutina y la comparación de resultados obtenidos en diferentes laboratorios.¹⁶²162. Grassi MFR , Olavarria VN, Kruschewsky RA, Yamano Y , Jacobson S, Taylor GP , et al. Utility of HTLV proviral load quantification in diagnosis of HTLV-1-associated myelopathy requires international standardization. J Clin Virol [Internet]. 2013 Nov [cited 2020 Oct 15] ; 58(3):584-6. Available from: https://doi.org/10.1016/j.jcv.2013.09.003
https://doi.org/10.1016/j.jcv.2013.09.00... ^,¹⁶³163. Kuramitsu M , Okuma K , Yamochi T , Sato T , Sasaki D , Hasegawa H, et al. Standardization of quantitative PCR for human T-cell leukemia virus type 1 in Japan: a collaborative study. J Clin Microbiol [Internet]. 2015 Nov [cited 2020 Oct 15] ; 53(11):3485-91. Available from: https://doi.org/10.1128/jcm.01628-15
https://doi.org/10.1128/jcm.01628-15... Algunos individuos infectados por HTLV-1/2 puede tener una carga proviral indetectable.¹⁶⁴164. Lee T-H, Chafets DM, Busch MP, Murphy EL . Quantitation of HTLV-I and II proviral load using real-time quantitative PCR with SYBR Green chemistry. J Clin Virol [Internet]. 2004 Dec [cited 2020 Oct 15] ; 31(4):275-82. Available from: https://doi.org/10.1016/j.jcv.2004.05.016
https://doi.org/10.1016/j.jcv.2004.05.01...

165. Rosadas C , Tosswill JH, Tedder R, Taylor GP . Pregnancy does not adversely impact diagnostic tests for HTLV-1/2 infection. PLoS Negl Trop Dis [Internet]. 2019 Sep [cited 2020 Oct 15] ; 13(9):e0007736. Available from: https://dx.doi.org/10.1371%2Fjournal.pntd.0007736
https://doi.org/10.1371%2Fjournal.pntd.0... ^-¹⁶⁶166. Montanheiro P , Olah I, Fukumori LMI, Smid J , Oliveira ACP , Kankaki LIB, et al. Low DNA HTLV-2 proviral load among women in São Paulo City. Virus Res [Internet]. 2008 Jul [cited 2020 Oct 15] ; 135(1):22-5. Available from: https://doi.org/10.1016/j.virusres.2008.01.015
https://doi.org/10.1016/j.virusres.2008.... En estos casos, es posible realizar la nPCR, que es más sensible que la RT-PCR. Otra alternativa es realizar una prueba serológica confirmatoria (si aún no se ha realizado) o solicitar muestras consecutivas para seguimiento.¹⁴⁸148. Martins ML, Santos ACS, Namen-Lopes MS, Barbosa-Stancioli EF, Utsch DG, Carneiro-Proietti ABF . Long-term serological follow-up of blood donors with an HTLV-Indeterminate Western Blot: Antibody Profile of Seroconverters and Individuals With False Reactions. J Med Virol [Internet]. 2010 Oct [cited 2020 Oct 15] ; 82(10):1746-53. Available from: https://doi.org/10.1002/jmv.21881
https://doi.org/10.1002/jmv.21881...

La duración de la ventana inmunológica en la infección por HTLV-1/2 se ha evidenciado en la aparición de anticuerpos entre los 16 y 39 días posteriores al trasplante de órganos, y el material genético proviral, entre los 16 y 23 días posteriores a la infección.¹⁶⁷167. Cook LBM , Melamed A , Demontis MA , Laydon DJ , Fox JM, Tosswill JHC , et al. Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients. Retrovirology [Internet]. 2016 Jan [cited 2020 Oct 15] ; 13:3. Available from: https://doi.org/10.1186/s12977-015-0236-7
https://doi.org/10.1186/s12977-015-0236-... En un estudio realizado con individuos infectados por transfusión de sangre se observó una seroconversión mediana de 51 días (36 a 72 días).²⁵25. Manns A, Wilks RJ, Murphy EL, Haynes G, Barnett M, Hanchard B, et al. A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion. Int J Cancer [Internet]. 1992 Jul [cited 2020 Oct 15] ; 51(6):886-91. Available from: https://doi.org/10.1002/ijc.2910510609
https://doi.org/10.1002/ijc.2910510609... Cabe señalar que las metodologías disponibles cuando se desarrolló este estudio no tenían la misma sensibilidad que los métodos de diagnóstico actuales.¹⁶⁸168. Murphy EL . Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): implications for blood transfusion safety. Transfus Clin Biol [Internet]. 2016 Feb [cited 2020 Oct 15] ; 23(1):13-9. Available from: https://doi.org/10.1016/j.tracli.2015.12.001
https://doi.org/10.1016/j.tracli.2015.12...

Tratamiento

La terapia de la infección por el HTLV-1 consiste en intervenciones dirigidas a las complicaciones resultantes de la enfermedad.¹⁶⁹169. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de manejo clínico da infecção pelo HTLV [Internet]. Brasilia: Ministério da Saúde; 2013 [citado 2019 fev 4]. Disponível em:http://www.sierj.org.br/artigos/htlv_manual_final_pdf_25082.pdf
http://www.sierj.org.br/artigos/htlv_man... ^,¹⁷⁰170. Ministério da Saúde (BR). Protocolo de uso zidovudina para tratamento do adulto com leucemia/linfoma associado ao Vírus HTLV-1 [Internet]. Brasília: Ministério da Saúde ; 2016 [citado 2020 out 15]. Disponível em:http://www.aids.gov.br/pt-br/pub/2016/protocolo-de-uso-da-zidovudina-para-tratamento-do-adulto-com-leucemialinfoma-associado-ao
http://www.aids.gov.br/pt-br/pub/2016/pr... En 2016, la Conitec,¹⁷⁰170. Ministério da Saúde (BR). Protocolo de uso zidovudina para tratamento do adulto com leucemia/linfoma associado ao Vírus HTLV-1 [Internet]. Brasília: Ministério da Saúde ; 2016 [citado 2020 out 15]. Disponível em:http://www.aids.gov.br/pt-br/pub/2016/protocolo-de-uso-da-zidovudina-para-tratamento-do-adulto-com-leucemialinfoma-associado-ao
http://www.aids.gov.br/pt-br/pub/2016/pr... y en 2019-2020, la Sociedad Internacional de Retrovirología, publicaron recomendaciones para el tratamiento de ATLL y HAM.¹⁷¹171. Cook L B, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, et al. Revised adult T-cell leukemia-lymphoma international consensus meeting report. J Clin Oncol [Internet]. 2019 Mar [cited 2020 Oct 15] ; 37(8):677-87. Available from: https://doi.org/10.1200/jco.18.00501
https://doi.org/10.1200/jco.18.00501... ^,¹⁷²172. Araujo A , Bangham CRM , Casseb J , Gotuzzo E , Jacobson S , Martin F, et al. Management of HAM/TSP. Neurol Clin Pract [Internet]. 2020 Mar [cited 2020 Oct 15] . Available from: https://doi.org/10.1212/CPJ.0000000000000832
https://doi.org/10.1212/CPJ.000000000000... El uso de zidovudina asociado al interferón alfa fue autorizado para el tratamiento de ATLL a través de la publicación de la Ordenanza MS/SVS nº 54, el 18 de julio de 2016.²2. Ministério da Saúde (BR). Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infeções sexualmente transmissíveis (IST) [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 jun 14]. Disponível em:http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes
http://www.aids.gov.br/pt-br/pub/2015/pr... ^,¹⁷⁰170. Ministério da Saúde (BR). Protocolo de uso zidovudina para tratamento do adulto com leucemia/linfoma associado ao Vírus HTLV-1 [Internet]. Brasília: Ministério da Saúde ; 2016 [citado 2020 out 15]. Disponível em:http://www.aids.gov.br/pt-br/pub/2016/protocolo-de-uso-da-zidovudina-para-tratamento-do-adulto-com-leucemialinfoma-associado-ao
http://www.aids.gov.br/pt-br/pub/2016/pr... Los esquemas terapéuticos varían de acuerdo con la presentación clínica, la progresión de los síntomas y la disponibilidad local de los medicamentos.

Las personas infectadas deben ser acompañadas al servicio especializado para recibir atención de apoyo sicológico, con atención especial para el diagnóstico de manifestaciones clínicas precoces de las diversas manifestaciones asociadas a la infección.

Vigilancia, prevención y control

Aunque haya sido descrita hace algunas décadas, la infección por el HTLV permanece relativamente desconocida por la población en general y por profesionales de salud. En los servicios que atienden a personas infectadas, el abordaje se debe enfocar no solo en los aspectos relacionados al riesgo de enfermar¹⁷³173. Zihlmann KF, Alvarenga AT, Casseb J . Living invisible: HTLV-1-Infected persons and the lack of care in public health. PLoS Negl Trop Dis [Internet]. 2012 [cited 2020 Oct 15] ; 6(6):e1705. Available from: https://doi.org/10.1371/journal.pntd.0001705
https://doi.org/10.1371/journal.pntd.000... y sí, también, en la orientación sobre prevención de la transmisión de la enfermedad.

Después de un diagnóstico positivo de infección por HTLV-1/2, se debe invitar a los contactos sexuales a someterse a un cribado serológico y derivar a los con pruebas positivas para recibir asesoramiento y seguimiento adecuado. Dicho asesoramiento debe incluir información sobre la cronicidad de la infección y la relevancia del seguimiento clínico a largo plazo.¹⁶⁹169. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Guia de manejo clínico da infecção pelo HTLV [Internet]. Brasilia: Ministério da Saúde; 2013 [citado 2019 fev 4]. Disponível em:http://www.sierj.org.br/artigos/htlv_manual_final_pdf_25082.pdf
http://www.sierj.org.br/artigos/htlv_man... ^,¹⁷⁴174. Centers for Disease Control and Prevention - CDC. Recommendations for counseling persons infected with human T-lymphotrophic virus, types I and II. MMWR [Internet]. 1993 Jun [cited 2020 Oct 15] ; 42(RR-9):1-13. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/00021234.htm
https://www.cdc.gov/mmwr/preview/mmwrhtm... Es importante aclarar las manifestaciones clínicas iniciales y su progresión, los mecanismos de transmisión y su prevención. No se recomienda la donación de sangre, semen, órganos sólidos o tejidos, bien como la lactancia.

En los servicios de atención a personas infectadas por HIV y otras ITS, es importante incluir el rastreo del HTLV rn la rutina del cuidado. La persona infectada por el HTLV debe ser orientada sobre el riesgo de la transmisión sexual, parejas sexuales serodiscordantes y uso de preservativo - este que puede dejar de usarse durante el período fértil, si hubiera deseo de quedar embarazada.¹⁷⁴174. Centers for Disease Control and Prevention - CDC. Recommendations for counseling persons infected with human T-lymphotrophic virus, types I and II. MMWR [Internet]. 1993 Jun [cited 2020 Oct 15] ; 42(RR-9):1-13. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/00021234.htm
https://www.cdc.gov/mmwr/preview/mmwrhtm...

En Brasil, dada la escasez de material disponible para los profesionales de la salud y la población en general, grupos académicos y organizaciones no gubernamentales han desarrollado varias iniciativas para difundir información sobre HTLV-1/2. Entre las organizaciones e iniciativas con este propósito se destacan: el Núcleo de Apoyo a la Investigación en Retrovirus (NAP-Retrovirus) de la Universidad de São Paulo; los Cuadernos de la Fundación Hemominas sobre la infección por HTLV; la Asociación HTLVida; y el Grupo Vitamóre - Asociación de los Portadores de HTLV.

La falta de un registro nacional de casos dificulta la comprensión del escenario real de infección en el país y, por lo tanto, la implementación de políticas específicas de salud pública. Cabe señalar que la notificación de casos es uno de los pilares de las acciones para enfrentar e investigar el HTLV-1 en países como Japón, Inglaterra, España y la isla de Martinica.¹⁷⁵175. Coler-Reilly ALG, Yagishita N , Suzuki H, Sato T , Araya N , Inoue E, et al. Nation-wide epidemiological study of Japanese patients with rare viral myelopathy using novel registration system (HAM-net). Orphanet J Rare Dis [Internet]. 2016 May [cited 2020 Oct 15] ; 11(1):69. Available from: https://doi.org/10.1186/s13023-016-0451-x
https://doi.org/10.1186/s13023-016-0451-...

176. Olindo S, Jeannin S, Saint-Vil M, Signate A, Edjmonana-Kaptue M, Joux J, Merle H, et al. Temporal trends in human T-lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) incidence in Martinique over 25 years (1986-2010). PLoS Negl Trop Dis [Internet]. 2018 Mar [cited 2020 Oct 15] ; 12(3):e0006304. Available from: https://doi.org/10.1371/journal.pntd.0006304
https://doi.org/10.1371/journal.pntd.000...

177. Brant LJ, Cawley C, Davison KL, Taylor GP , the HTLV National Register Steering C. Recruiting individuals into the HTLV cohort study in the United Kingdom: clinical findings and challenges in the first six years, 2003 to 2009. Euro Surveill [Internet]. 2011 Nov [cited 2020 Oct 15] ; 16(46):20017. Available from: https://doi.org/10.2807/ese.16.46.20017-en
https://doi.org/10.2807/ese.16.46.20017-... ^-¹⁷⁸178. Mendoza C, Pirón M, Gonzalez R, Jiménez A, Caballero E, Roc L, et al. Clinical presentation of individuals with human T-cell leukemia virus type-1 infection in Spain. Open Forum Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 6(2):ofz036. Available from: https://doi.org/10.1093/ofid/ofz036
https://doi.org/10.1093/ofid/ofz036...

Poblaciones especiales

Gestantes

En Brasil, la prevalencia de HTLV-1/2 en gestantes puede llegar al 1% en determinadas regiones del país (Tabla 1).¹⁵⁹159. Medeiros ACM, Vidal LRR, Von Linsingen R, Ferin AN, Strapasson TB, Almeida SM, et al. Confirmatory molecular method for HTLV-1/2 infection in high-risk pregnant women. J Med Virol [Internet]. 2018 May [cited 2020 Oct 15] ; 90(5):998-1001. Available from: https://doi.org/10.1002/jmv.25014
https://doi.org/10.1002/jmv.25014... ^,¹⁷⁹179. Moura AA, Mello MJG, Correia JB. Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population. Int J Infect Dis [Internet]. 2015 Oct [cited 2020 Oct 15] ; 39: 10-5. Available from: https://doi.org/10.1016/j.ijid.2015.07.022
https://doi.org/10.1016/j.ijid.2015.07.0...

180. Figueiró-Filho EA, Senefonte FRA, Lopes AHA, Morais OO, Souza Júnior VG, Maia TL, et al. Freqüência das infecções pelo HIV-1, rubéola, sífilis, toxoplasmose, citomegalovírus, herpes simples, hepatite B, hepatite C, doença de Chagas e HTLV I/II em gestantes, do Estado de Mato Grosso do Sul. Rev Soc Bras Med Trop [Internet]. 2007 mar-abr [citado 2020 out 15]; 40(2):181-7. Disponível em: https://doi.org/10.1590/S0037-86822007000200007
https://doi.org/10.1590/S0037-8682200700...

181. Oliveira SR, Avelino MM. Soroprevalência do vírus linfotrópico-T humano tipo I entre gestantes em Goiânia, GO, Brasil. Rev Bras Ginecol Obstet [Internet]. 2006 [citado 2020 out 15]; 28(8):467-72. Disponível em: https://doi.org/10.1590/S0100-72032006000800005
https://doi.org/10.1590/S0100-7203200600...

182. Olbrich-Neto J, Meira DA. Soroprevalence of HTLV-I/II, HIV, siphylis and toxoplasmosis among pregnant women seen at Botucatu - São Paulo - Brazil: risk factors for HTLV-I/II infection. Rev Soc Bras Med Trop [Internet]. 2004 [cited 2020 Oct 15] ; 37(1):28-32. Available from: https://doi.org/10.1590/S0037-86822004000100008
https://doi.org/10.1590/S0037-8682200400...

183. Bittencourt AL, Dourado I, Filho PB, Santos M, Valadão E, Alcantara LC, et al. Human T-cell lymphotropic virus type 1 infection among pregnant women in northeastern Brazil. J Acquir Immune Defic Syndr [Internet]. 2001 Mar [cited 2020 Oct 15] ; 26(5):490-4. Available from: https://doi.org/10.1097/00126334-200104150-00016
https://doi.org/10.1097/00126334-2001041...

184. Broutet N, Queiroz Sousa A, Basilio FP, Sa HL, Simon F, Dabis F. Prevalence of HIV-1, HIV-2 and HTLV antibody, in Fortaleza, Ceara, Brazil, 1993-1994. Int J STD AIDS [Internet]. 1996 Aug-Sep [cited 2020 Oct 15] ; 7(5):365-9. Available from: https://doi.org/10.1258/0956462961918103
https://doi.org/10.1258/0956462961918103...

185. Santos JI, Lopes MA, Deliège-Vasconcelos E, Couto-Fernandez JC, Patel BN, Barreto ML , et al. Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia. Rev Inst Med Trop São Paulo [Internet]. 1995 Jul-Aug [cited 2020 Oct 15] ; 37(4):343-8. Available from: https://doi.org/10.1590/S0036-46651995000400010
https://doi.org/10.1590/S0036-4665199500...

186. Mendes FCM, Lima JRO, Melo BO, Pinto CMFS, Maia HS, Ferro TAF, et al. Molecular detection of human T cell lymphotropic virus type 1 in pregnant women from Maranhão state, Brazil. Braz J Microbiol [Internet]. 2020 Jun [cited 2020 Oct 15] ; 51(2):637-45. Available from: https://doi.org/10.1007/s42770-020-00233-0
https://doi.org/10.1007/s42770-020-00233...

187. Sodré Barmpas DB, Monteiro DLM, Taquette SR, Rodrigues NCP, Trajano AJB, Cunha JC, et al. Pregnancy outcomes and mother-to-child transmission rate in HTLV-1/2 infected women attending two public hospitals in the metropolitan area of Rio de Janeiro. PLoS Negl Trop Dis [Internet]. 2019 Jun [cited 2020 Oct 15] ; 13(6):e0007404. Available from: https://doi.org/10.1371/journal.pntd.0007404
https://doi.org/10.1371/journal.pntd.000...

188. Guerra AB, Siravenha LQ, Laurentino RV, Feitosa RNM, Azecedo VN, Vallinoto ACR , et al. Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Belém, Pará, Northern Brazil. BMC Pregnancy Childbirth [Internet]. 2018 May [cited 2020 Oct 15] ; 18(1):169. Available from: https://doi.org/10.1186/s12884-018-1753-x
https://doi.org/10.1186/s12884-018-1753-...

189. Monteiro DLM, Taquette SR, Sodré Barmpas DB, Rodrigues NCP, Teixeira SAM, Villela LHC, et al. Prevalence of HTLV-1/2 in pregnant women living in the metropolitan area of Rio de Janeiro. PLoS Negl Trop Dis [Internet]. 2014 Sep [cited 2020 Oct 15] ; 8:e3146. Available from: https://doi.org/10.1371/journal.pntd.0003146
https://doi.org/10.1371/journal.pntd.000...

190. Boa-Sorte N , Purificação A, Amorim T, Assunção L, Reis A, Galvão-Castro B . Dried blood spot testing for the antenatal screening of HTLV, HIV, syphilis, toxoplasmosis and hepatitis B and C: prevalence, accuracy and operational aspects. Brazilian J Infect Dis [Internet]. 2014 Nov-Dec [cited 2020 Oct 15] ; 18(6):618-24. Available from: https://doi.org/10.1016/j.bjid.2014.05.009
https://doi.org/10.1016/j.bjid.2014.05.0...

191. Mello MAG, Conceição AF, Sousa SMB, Alcântara LC, Marin LJ, Raiol MRS, et al. HTLV-1 in pregnant women from the Southern Bahia, Brazil: a neglected condition despite the high prevalence. Virol J [Internet]. 2014 Feb [cited 2020 Oct 15] ; 11:28. Available from: https://doi.org/10.1186/1743-422X-11-28
https://doi.org/10.1186/1743-422X-11-28...

192. Sequeira CG, Tamegão-Lopes BP, Santos EJM, Ventura AMR, Moraes-Pinto MI, Succi RCM. Estudo descritivo da infecção pelo HTLV em uma população de gestantes do Estado do Pará, norte do Brasil. Rev Soc Bras Med Trop [Internet]. 2012 [citado 2020 out 15]; 45(4):453-6. Disponível em: https://doi.org/10.1590/S0037-86822012005000007
https://doi.org/10.1590/S0037-8682201200...

193. Souza VG, Martins ML , Carneiro-Proietti ABF , Januário JN, Ladeira RVP, Silva CMS, et al. High prevalence of HTLV-1 and 2 viruses in pregnant women in São Luis, state of Maranhão, Brazil. Rev Soc Bras Med Trop [Internet]. 2012 Mar-Apr [cited 2020 Oct 15] ; 45(2):159-62. Available from: https://doi.org/10.1590/S0037-86822012000200004
https://doi.org/10.1590/S0037-8682201200...

194. Machado-Filho AC, Sardinha JFJ, Ponte RL, Costa EP, da Silva SS, Martinez-Espinosa FE. Prevalence of infection for HIV, HTLV, HBV and of syphilis and chlamydia in pregnant women in a tertiary health unit in the western Brazilian Amazon region. Rev Bras Ginecol Obstet [Internet]. 2010 Apr [cited 2020 Oct 15] ; 32(4):176-83. Available from: https://doi.org/10.1590/S0100-72032010000400005
https://doi.org/10.1590/S0100-7203201000...

195. Magalhães T, Mota-Miranda AC, Alcantara LCJ, Olavarria V, Galvão-Castro B , Rios-Grassi MF. Phylogenetic and molecular analysis of HTLV-1 isolates from a medium sized town in Northern of Brazil: Tracing a common origin of the virus from the most endemic city in the country. J Med Virol [Internet]. 2008 Nov [cited 2020 Oct 15] ; 80(11):2040-5. Available from: https://doi.org/10.1002/jmv.21278
https://doi.org/10.1002/jmv.21278... ^-¹⁹⁶196. Dal Fabbro MMFJ, Cunha RV, Bóia MN, Portela P, Botelho CA, Freitas GMB, et al. Infecção pelo HTLV 1/2: atuação no pré-natal como estratégia de controle da doença no Estado de Mato Grosso do Sul. Rev Soc Bras Med Tro p [Internet]. 2008 Mar-Apr [cited 2020 Oct 15] ; 41(2):148-51. Available from: https://doi.org/10.1590/S0037-86822008000200003
https://doi.org/10.1590/S0037-8682200800... A pesar de la existencia de reportes sobre el desarrollo de enfermedades asociadas al HTLV durante el embarazo (HAM, ATLL), no hay evidencia consistente sobre el impacto de la infección en el ciclo embarazo-puerperal.²³23. Rosadas C, Taylor GP. Mother-to-child HTLV-1 transmission: unmet research needs. Front Microbiol [Internet]. 2019 May [cited 2020 Oct 15] ; 10:999. Available from: https://doi.org/10.3389/fmicb.2019.00999
https://doi.org/10.3389/fmicb.2019.00999... Sin embargo, la infección infantil se asocia con un mayor riesgo de desarrollar enfermedades asociadas con HTLV-1, con énfasis en ATLL, que es altamente letal.²³23. Rosadas C, Taylor GP. Mother-to-child HTLV-1 transmission: unmet research needs. Front Microbiol [Internet]. 2019 May [cited 2020 Oct 15] ; 10:999. Available from: https://doi.org/10.3389/fmicb.2019.00999
https://doi.org/10.3389/fmicb.2019.00999... ^,¹⁹⁷197. The T and B-cell malignancy study group. The third nation-wide study on adult T-cell leukemia/lymphoma (ATL) in Japan: characteristic patterns of HLA antigen and HTLV-I infection in ATL patients and their relatives. The T- and B-cell Malignancy Study Group. Int J Cancer [Internet]. 1988 Apr [cited 2020 Oct 15] ; 41(4):505-12. Available from: https://doi.org/10.1002/ijc.2910410406
https://doi.org/10.1002/ijc.2910410406... ^,¹⁹⁸198. Bartholomew C, Jack N, Edwards J, Charles W, Corbin D, Cleghorn FR, et al. HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. J Hum Virol. 1998 May-Jun;1(4):302-5. Por lo tanto, la prevención de la transmisión vertical es de extrema importancia para reducir la incidencia de enfermedades asociadas al virus.²³23. Rosadas C, Taylor GP. Mother-to-child HTLV-1 transmission: unmet research needs. Front Microbiol [Internet]. 2019 May [cited 2020 Oct 15] ; 10:999. Available from: https://doi.org/10.3389/fmicb.2019.00999
https://doi.org/10.3389/fmicb.2019.00999... ^,⁹⁶96. Rosadas C , Puccioni-Sohler M , Oliveira ACP , Casseb J , Sousa M, Taylor GP . Adult T-cell leukaemia/lymphoma in Brazil: a rare disease or rarely diagnosed? Br J Haematol [Internet]. 2020 Feb [cited 2020 Oct 15] ; 188(4):e46-9. Available from: https://doi.org/10.1111/bjh.16318
https://doi.org/10.1111/bjh.16318... ^,¹³⁷137. Puccioni-Sohler M , Grassi MFR , Galvão-Castro B, Caterino A, Proietti ABFC, Vicente ACP , et al. Increasing awareness of human T-lymphotropic virus type-1 infection: a serious, invisible, and neglected health problem in Brazil. Rev Soc Bras Med Trop [Internet]. 2019 Oct [cited 2020 Oct 15] ; 52:e20190343. Available from: http://dx.doi.org/10.1590/0037-8682-0343-2019
https://doi.org/10.1590/0037-8682-0343-2...

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Tabla 1
Prevalencia de la infección por el HTLV-1/2 en gestantes, en diferentes estados de Brasil

Como se sabe que la lactancia materna es la principal vía de transmisión vertical del HTLV-1/2¹³⁵135. Itabashi K, Miyazawa T, Sekizawa A, Tokita A, Saito S, Moriuchi H, et al. A nationwide antenatal human T-cell leukemia virus type-1 antibody screening in Japan. Front Microbiol [Internet]. 2020 Apr [cited 2020 Oct 15] ; 11:595. Available from: https://dx.doi.org/10.3389%2Ffmicb.2020.00595
https://doi.org/10.3389%2Ffmicb.2020.005... ^,¹⁹⁹199. Hino S. Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki. Proc Jpn Acad Ser B Phys Biol Sci [Internet]. 2011 [cited 2020 Oct 15] ; 87(4):152-66. Available from: https://doi.org/10.2183/pjab.87.152
https://doi.org/10.2183/pjab.87.152...

200. Ureta-Vidal A, Angelin-Duclos C, Tortevoye P, Murphy E, Lepere JF, Buigues RP, et al. Mother-to-child transmission of human T-cell-leukemia/lymphoma virus type I: Implication of high antiviral antibody titer and high proviral load in carrier mothers. Int J Cancer [Internet]. 1999 Sep [cited 2020 Oct 15] ; 82(6):832-6. Available from: https://doi.org/10.1002/(sici)1097-0215(19990909)82:6%3C832::aid-ijc11%3E3.0.co;2-p
https://doi.org/10.1002/(sici)1097-0215(...

201. Oki T, Yoshinaga M, Otsuka H, Miyata K, Sonoda S, Nagata Y. A sero-epidemiological study on mother-to-child transmission of HTLV-I in southern Kyushu, Japan. Asia-Oceania J Obstet Gynaecol [Internet]. 1992 Dec [cited 2020 Oct 15] ; 18(4):371-7. Available from: https://doi.org/10.1111/j.1447-0756.1992.tb00333.x
https://doi.org/10.1111/j.1447-0756.1992...

202. Takahashi K, Takezaki T, Oki T, Kawakami K, Yashiki S, Fujiyoshi T, et al. Inhibitory effect of maternal antibody on mother-to-child transmission of human T-lymphotropic virus type I. Int J Cancer [Internet]. 1991 Nov [cited 2020 Oct 15] ; 49(5):673-7. Available from: https://doi.org/10.1002/ijc.2910490508
https://doi.org/10.1002/ijc.2910490508...

203. Ando Y, Matsumoto Y, Nakano S, Saito K, Kakimoto K, Tanigawa T, et al. Long-term follow-up study of HTLV-I infection in bottle-fed children born to seropositive mothers. J Infect [Internet]. 2003 Jan [cited 2020 Oct 15] ; 46(1):9-11. Available from: https://doi.org/10.1053/jinf.2002.1081
https://doi.org/10.1053/jinf.2002.1081... ^-²⁰⁴204. Nishijima T, Shimada S, Noda H, Miyake K. Towards the elimination of HTLV-1 infection in Japan. Lancet Infect Dis [Internet]. 2019 Jan [cited 2020 Oct 15] ; 19(1):15-6. Available from: https://doi.org/10.1016/S1473-3099(18)30735-7
https://doi.org/10.1016/S1473-3099(18)30... y aún no existe una vacuna para combatir la infección, ni siquiera un tratamiento curativo, la lactancia materna no está contraindicada en madres infectadas por el virus. Para estas mujeres, se recomienda el uso de inhibidores de la lactancia y el suministro de fórmulas lácteas infantiles.²2. Ministério da Saúde (BR). Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infeções sexualmente transmissíveis (IST) [Internet]. Brasília: Ministério da Saúde; 2020 [citado 2020 jun 14]. Disponível em:http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes
http://www.aids.gov.br/pt-br/pub/2015/pr... Aunque el SUS no prevé la detección de la infección por HTLV-1/2 en la atención prenatal, se recomiendan las pruebas de detección del virus en gestantes, seguido del acogimiento a las mujeres infectadas y sus familiares, lo que permite la implementación efectiva de medidas de prevención de la transmisión.

Poblaciones indígenas

Las vías de transmisión vertical y sexual son importantes para el mantenimiento del HTLV en comunidades epidemiológicamente cerradas o semicerradas, como es el caso del HTLV-2c, que es prevalente entre los pueblos indígenas que viven en la Amazonía brasileña y en áreas urbanas.¹²12. Ishak R, Harrington WJ, Azevedo VN, Eiraku N, Ishak MO, Guerreiro JF, et al. Identification of human T cell lymphotropic virus type IIa infection in the Kayapo, an indigenous population of Brazil. AIDS Res Hum Retroviruses [Internet]. 1995 Jul [cited 2020 Oct 15] ; 11(7):813-21. Available from: https://doi.org/10.1089/aid.1995.11.813
https://doi.org/10.1089/aid.1995.11.813... ^,¹³13. Eiraku N , Novoa P, Costa Ferreira M, Monken C, Ishak R , Costa Ferreira O, et al. Identification and characterization of a new and distinct molecular subtype of human T-cell lymphotropic virus type 2. J Virol [Internet]. 1996 Mar [cited 2020 Oct 15] ; 70(3):1481-92. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC189969/^,²⁰⁵205. Ishak R , Vallinoto AC, Azevedo VN , Lewis M , Hall WW , GuimarãesIshak MO . Molecular evidence of mother-to-child transmission of HTLV-IIc in the Kararao Village (Kayapo) in the Amazon region of Brazil. Rev Soc Bras Med Trop [Internet]. 2001 Nov-Dec [cited 2020 Oct 5]; 34(6):519-25. Available from: http://dx.doi.org/10.1590/S0037-86822001000600004
https://doi.org/10.1590/S0037-8682200100...

206. Silva EA, Otsuki K, Leite ACB, Alamy AH, Sa D, Vicente ACP . HTLV-II Infection associated with a chronic neurodegenerative disease: clinical and molecular analysis. J Med Virol [Internet]. 2002 Feb [cited 2020 Oct 15] ; 66(2):253-7. Available from: https://doi.org/10.1002/jmv.2138
https://doi.org/10.1002/jmv.2138...

207. Catalan-Soares B, Barbosa-Stancioli EF , Alcantara LCJ , et al. HTLV-2 Horizontal and vertical transmission in a family from a Brazilian urban area: seroepidemiological, clinical and molecular study. AIDS Res Hum Retroviruses [Internet]. 2005 Jun [cited 2020 Oct 15] ; 21(6):521-6. Available from: https://doi.org/10.1089/aid.2005.21.521
https://doi.org/10.1089/aid.2005.21.521...

208. Renner JDP, Laurino JP, Menna-Barreto M, Schmitt VM. Molecular evidence of HTLV-II subtype B among an urban population living in South Brazil. AIDS Res Hum Retroviruses [Internet]. 2006 Apr [cited 2020 Oct 15] ; 22(4):301-6. Available from: https://doi.org/10.1089/aid.2006.22.301
https://doi.org/10.1089/aid.2006.22.301... ^-²⁰⁹209. Ishak R , Ishak MO , Azevedo VN , Santos DEM, Vallinoto ACR , Saraiva JCP, et al. Detection of HTLV-IIa blood donors in an urban area of the Amazon Region of Brazil (Belém, PA). Rev Soc Bras Med Trop [Internet]. 1998 Mar-Apr [cited 2020 Oct 15] ; 31(2):193-7. Available from: http://dx.doi.org/10.1590/S0037-86821998000200005
https://doi.org/10.1590/S0037-8682199800... Cabe recordar que la infección intrafamiliar en las comunidades Kayapó se expresa en la transmisión del virus entre dos o tres generaciones, y en más del 20% de los niños menores de nueve años infectados.¹²12. Ishak R, Harrington WJ, Azevedo VN, Eiraku N, Ishak MO, Guerreiro JF, et al. Identification of human T cell lymphotropic virus type IIa infection in the Kayapo, an indigenous population of Brazil. AIDS Res Hum Retroviruses [Internet]. 1995 Jul [cited 2020 Oct 15] ; 11(7):813-21. Available from: https://doi.org/10.1089/aid.1995.11.813
https://doi.org/10.1089/aid.1995.11.813... La transmisión vertical mantiene al virus en alta endemicidad, ya que los procedimientos habituales para no amamantar por parte de madres infectadas comúnmente no son seguidos.²⁰⁵205. Ishak R , Vallinoto AC, Azevedo VN , Lewis M , Hall WW , GuimarãesIshak MO . Molecular evidence of mother-to-child transmission of HTLV-IIc in the Kararao Village (Kayapo) in the Amazon region of Brazil. Rev Soc Bras Med Trop [Internet]. 2001 Nov-Dec [cited 2020 Oct 5]; 34(6):519-25. Available from: http://dx.doi.org/10.1590/S0037-86822001000600004
https://doi.org/10.1590/S0037-8682200100... La mayor evidencia de enfermedades asociadas con HTLV-2⁵5. Kalyanaraman VS , Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC . A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science [Internet]. 1982 Nov [cited 2020 Oct 15]; 218(4572):571-3. Available from: https://doi.org/10.1126/science.6981847
https://doi.org/10.1126/science.6981847... ^,⁴³43. Hjelle B, Appenzeller O, Mills R, Appenzeller O, Jahnke R, Alexander S, et al. Chronic neurodegenerative disease associated with HTLV-II infection. Lancet [Internet]. 1992 Mar [cited 2020 Oct 15] ; 339(8794):645-6. Available from: https://doi.org/10.1016/0140-6736(92)90797-7
https://doi.org/10.1016/0140-6736(92)907...

44. Zucker-Franklin D, Hooper WC, Evatt BL. Human lymphotropic retroviruses associated with mycosis fungoides: evidence that human T-cell lymphotropic virus type II (HTLV-II) as well as HTLV-I may play a role in the disease. Blood [Internet]. 1992 Sep [cited 2020 Oct 15] ; 80(6):1537-45. Available from: https://pubmed.ncbi.nlm.nih.gov/1520878 /
https://pubmed.ncbi.nlm.nih.gov/1520878...

45. Maytal J, Horowitz S, Lipper S, Poiesz B, Wang CY, Siegal FP. Progressive nemaline rod myopathy in a woman coinfected with HIV-1 and HTLV-2. Mt Sinai J Med. 1993 May; 60(3):242-6.

46. Peters AA, Oger JJ, Coulthart MB, Waters DJ, Cummings HJ, Dekaban GA. An apparent case of human T-cell lymphotropic virus type II (HTLV-II)-associated neurological disease: a clinical, molecular, and phylogenetic characterisation. J Clin Virol [Internet]. 1999 Sep [cited 2020 Oct 15] ; 14(1):37-50. Available from: https://doi.org/10.1016/S1386-6532(99)00041-4
https://doi.org/10.1016/S1386-6532(99)00...

47. Araujo A, Hall WW . Human T-Lymphotropic virus type ii and neurological disease. Ann Neurol [Internet]. 2004 Jul [cited 2020 Oct 15] ; 56(1):10-9. Available from: https://doi.org/10.1002/ana.20126
https://doi.org/10.1002/ana.20126... ^-⁴⁸48. Rosadas C , Vicente ACP, Zanella L, Cabral-Castro MJ, Peralta JM, Puccioni-Sohler M. Human T-lymphotropic virus type 2 subtype b in a patient with chronic neurological disorder. J Neurovirol [Internet]. 2014 Dec [cited 2020 Oct 15] ; 20(6):636-9. Available from: https://doi.org/10.1007/s13365-014-0280-4
https://doi.org/10.1007/s13365-014-0280-... requiere atención especial a las comunidades indígenas ubicadas en áreas de alta endemicidad de virus en la Amazonía brasileña.³⁹39. Ishak R , Ishak MO, Vallinoto ACR . The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil. Retrovirology [Internet]. 2020 Feb [cited 2020 Oct 15] ; 17:4. Available from: https://dx.doi.org/10.1186%2Fs12977-020-0512-z
https://doi.org/10.1186%2Fs12977-020-051...

Conclusiones

A pesar de que se descuida la infección por HTLV, Brasil tiene iniciativas destinadas a combatir la infección y la enfermedad por HTLV-1. Las enfermedades con consecuencias clínicas relevantes, como la mielopatía asociada al HTLV-1 y la leucemia/linfoma de células T, pueden reducirse con el acceso a servicios en el SUS. Los casos de baja complejidad pueden ser seguidos en los centros de salud y, cuando sea necesario, remitidos a centros especializados, para su tratamiento, rehabilitación y apoyo social. A pesar de las graves consecuencias que puede tener la infección en la vida de las personas, su control sigue representando un desafío para la salud pública. Los estudios epidemiológicos nacionales, el desarrollo de pruebas diagnósticas comerciales y protocolos clínicos con nuevas opciones terapéuticas pueden contribuir a la definición de políticas públicas y acciones específicas en el abordaje, prevención, control y tratamiento adecuados de la infección por HTLV-1/2 en Brasil.

Agradecimiento

A los miembros del grupo técnico de especialistas responsables por la elaboración del PCDT para Atención Integral a las Personas con ITS en 2020.

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Fechas de Publicación

Publicación en esta colección
15 Mar 2021
Fecha del número
2021

Histórico

Recibido
16 Jul 2020
Acepto
07 Oct 2020

Este é um artigo publicado em acesso aberto sob uma licença Creative Commons

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Clasificación y frecuencia	Manifestaciones clínicas	Sobrevida mediana	Diagnóstico	Otros hallazgos
Aguda (42 a 47%)	Forma leucémica, agresiva, leucometría, linfonodomegalia generalizada.	6 meses	Necesita confirmación histológica si <5% de linfocitos anormales	Hipercalcemia, fracturas, dolores óseos, exantema cutáneo, elevación de fosfatase alcalina sin causa aparente
Aguda (42 a 47%)	Lesiones de la piel, óseas, infiltrados pulmonares, comprometimiento del sistema nervioso central^a (10% de los casos).	6 meses
Linfomatosa (19%)	Curso rápido, linfadenopatía, hepatoesplenomegalia, lesiones de piel como exantema eritematoso, pápulas y nódulos.	10 meses	Necesita confirmación histológica si <5% de linfocitos anormales	Hipercalcemia menos frecuente, raras células tumorales circulantes
Crónica (19%): favorable (indolente)	Curso lento, exantema cutâneo esfoliativo, linfocitose absoluta por linfócitos T.	4 anos	Necessita confirmação histológica se <5% de linfócitos anormais	Células em flor podem ser observadas, lactato desidrogenase aumentada, hipercalcemia ausente
Desfavorable	Curso rápido.	15 meses	Necesita confirmación histológica si <5% de linfocitos anormales	Urea e lactato deshidrogenasa aumentadas, albúmina disminuida, células en flor pueden observarse
Smoldering (6%)	Curso lento, leucometría normal, lesiones de piel y pulmón.	4 años	Necesita confirmación histológica si <5% de linfocitos anormales	Células en flor pueden ser observadas (5% o más) en la sangre periférica, sin hipercalcemia

Región/Estado	Prevalencia (%)	n	Referencia^a
Norte
Pará	0,6	324	Guerra et al. 2018¹⁸⁸188. Guerra AB, Siravenha LQ, Laurentino RV, Feitosa RNM, Azecedo VN, Vallinoto ACR , et al. Seroprevalence of HIV, HTLV, CMV, HBV and rubella virus infections in pregnant adolescents who received care in the city of Belém, Pará, Northern Brazil. BMC Pregnancy Childbirth [Internet]. 2018 May [cited 2020 Oct 15] ; 18(1):169. Available from: https://doi.org/10.1186/s12884-018-1753-x https://doi.org/10.1186/s12884-018-1753-... ^b
Pará	0,3	13.382	Sequeira et al. 2012¹⁹²192. Sequeira CG, Tamegão-Lopes BP, Santos EJM, Ventura AMR, Moraes-Pinto MI, Succi RCM. Estudo descritivo da infecção pelo HTLV em uma população de gestantes do Estado do Pará, norte do Brasil. Rev Soc Bras Med Trop [Internet]. 2012 [citado 2020 out 15]; 45(4):453-6. Disponível em: https://doi.org/10.1590/S0037-86822012005000007 https://doi.org/10.1590/S0037-8682201200...
Amazonas	0	674	Machado Filho et al. 2010¹⁹⁴194. Machado-Filho AC, Sardinha JFJ, Ponte RL, Costa EP, da Silva SS, Martinez-Espinosa FE. Prevalence of infection for HIV, HTLV, HBV and of syphilis and chlamydia in pregnant women in a tertiary health unit in the western Brazilian Amazon region. Rev Bras Ginecol Obstet [Internet]. 2010 Apr [cited 2020 Oct 15] ; 32(4):176-83. Available from: https://doi.org/10.1590/S0100-72032010000400005 https://doi.org/10.1590/S0100-7203201000...
Nordeste
Alagoas	0,2	54.813	Moura et al. 2015¹⁷⁹179. Moura AA, Mello MJG, Correia JB. Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population. Int J Infect Dis [Internet]. 2015 Oct [cited 2020 Oct 15] ; 39: 10-5. Available from: https://doi.org/10.1016/j.ijid.2015.07.022 https://doi.org/10.1016/j.ijid.2015.07.0...
Bahia	0,14	692	Boa-Sorte et al. 2014¹⁹⁰190. Boa-Sorte N , Purificação A, Amorim T, Assunção L, Reis A, Galvão-Castro B . Dried blood spot testing for the antenatal screening of HTLV, HIV, syphilis, toxoplasmosis and hepatitis B and C: prevalence, accuracy and operational aspects. Brazilian J Infect Dis [Internet]. 2014 Nov-Dec [cited 2020 Oct 15] ; 18(6):618-24. Available from: https://doi.org/10.1016/j.bjid.2014.05.009 https://doi.org/10.1016/j.bjid.2014.05.0... ^c
	1,05	2.766	Mello et al. 2014¹⁹¹191. Mello MAG, Conceição AF, Sousa SMB, Alcântara LC, Marin LJ, Raiol MRS, et al. HTLV-1 in pregnant women from the Southern Bahia, Brazil: a neglected condition despite the high prevalence. Virol J [Internet]. 2014 Feb [cited 2020 Oct 15] ; 11:28. Available from: https://doi.org/10.1186/1743-422X-11-28 https://doi.org/10.1186/1743-422X-11-28...
	0,98	408	Magalhães et al. 2008¹⁹⁵195. Magalhães T, Mota-Miranda AC, Alcantara LCJ, Olavarria V, Galvão-Castro B , Rios-Grassi MF. Phylogenetic and molecular analysis of HTLV-1 isolates from a medium sized town in Northern of Brazil: Tracing a common origin of the virus from the most endemic city in the country. J Med Virol [Internet]. 2008 Nov [cited 2020 Oct 15] ; 80(11):2040-5. Available from: https://doi.org/10.1002/jmv.21278 https://doi.org/10.1002/jmv.21278...
	0,84	6.754	Bittencourt et al. 2001¹⁸³183. Bittencourt AL, Dourado I, Filho PB, Santos M, Valadão E, Alcantara LC, et al. Human T-cell lymphotropic virus type 1 infection among pregnant women in northeastern Brazil. J Acquir Immune Defic Syndr [Internet]. 2001 Mar [cited 2020 Oct 15] ; 26(5):490-4. Available from: https://doi.org/10.1097/00126334-200104150-00016 https://doi.org/10.1097/00126334-2001041...
	0,88	1.024	Santos et al. 1995¹⁸⁵185. Santos JI, Lopes MA, Deliège-Vasconcelos E, Couto-Fernandez JC, Patel BN, Barreto ML , et al. Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia. Rev Inst Med Trop São Paulo [Internet]. 1995 Jul-Aug [cited 2020 Oct 15] ; 37(4):343-8. Available from: https://doi.org/10.1590/S0036-46651995000400010 https://doi.org/10.1590/S0036-4665199500...
Maranhão	0,7	713	Mendes et al. 2020¹⁸⁶186. Mendes FCM, Lima JRO, Melo BO, Pinto CMFS, Maia HS, Ferro TAF, et al. Molecular detection of human T cell lymphotropic virus type 1 in pregnant women from Maranhão state, Brazil. Braz J Microbiol [Internet]. 2020 Jun [cited 2020 Oct 15] ; 51(2):637-45. Available from: https://doi.org/10.1007/s42770-020-00233-0 https://doi.org/10.1007/s42770-020-00233...
Maranhão	0,3	2.044	Guimarães de Souza et al. 2012¹⁹³193. Souza VG, Martins ML , Carneiro-Proietti ABF , Januário JN, Ladeira RVP, Silva CMS, et al. High prevalence of HTLV-1 and 2 viruses in pregnant women in São Luis, state of Maranhão, Brazil. Rev Soc Bras Med Trop [Internet]. 2012 Mar-Apr [cited 2020 Oct 15] ; 45(2):159-62. Available from: https://doi.org/10.1590/S0037-86822012000200004 https://doi.org/10.1590/S0037-8682201200...
Ceará	0,12	814	Broutet et al. 1996¹⁸⁴184. Broutet N, Queiroz Sousa A, Basilio FP, Sa HL, Simon F, Dabis F. Prevalence of HIV-1, HIV-2 and HTLV antibody, in Fortaleza, Ceara, Brazil, 1993-1994. Int J STD AIDS [Internet]. 1996 Aug-Sep [cited 2020 Oct 15] ; 7(5):365-9. Available from: https://doi.org/10.1258/0956462961918103 https://doi.org/10.1258/0956462961918103...
Centro-Oeste
Mato Grosso do Sul	0,13	116.689	Dal Fabbro et al. 2008¹⁹⁶196. Dal Fabbro MMFJ, Cunha RV, Bóia MN, Portela P, Botelho CA, Freitas GMB, et al. Infecção pelo HTLV 1/2: atuação no pré-natal como estratégia de controle da doença no Estado de Mato Grosso do Sul. Rev Soc Bras Med Tro p [Internet]. 2008 Mar-Apr [cited 2020 Oct 15] ; 41(2):148-51. Available from: https://doi.org/10.1590/S0037-86822008000200003 https://doi.org/10.1590/S0037-8682200800...
Mato Grosso do Sul	0,1	32.512	Figueiró Filho et al. 2007¹⁸⁰180. Figueiró-Filho EA, Senefonte FRA, Lopes AHA, Morais OO, Souza Júnior VG, Maia TL, et al. Freqüência das infecções pelo HIV-1, rubéola, sífilis, toxoplasmose, citomegalovírus, herpes simples, hepatite B, hepatite C, doença de Chagas e HTLV I/II em gestantes, do Estado de Mato Grosso do Sul. Rev Soc Bras Med Trop [Internet]. 2007 mar-abr [citado 2020 out 15]; 40(2):181-7. Disponível em: https://doi.org/10.1590/S0037-86822007000200007 https://doi.org/10.1590/S0037-8682200700...
Goiás	0,1	15.485	Oliveira et al. 2006¹⁸¹181. Oliveira SR, Avelino MM. Soroprevalência do vírus linfotrópico-T humano tipo I entre gestantes em Goiânia, GO, Brasil. Rev Bras Ginecol Obstet [Internet]. 2006 [citado 2020 out 15]; 28(8):467-72. Disponível em: https://doi.org/10.1590/S0100-72032006000800005 https://doi.org/10.1590/S0100-7203200600...
Sudeste
Rio de Janeiro	0,74	1.628	Barmpas et al. 2019¹⁸⁷187. Sodré Barmpas DB, Monteiro DLM, Taquette SR, Rodrigues NCP, Trajano AJB, Cunha JC, et al. Pregnancy outcomes and mother-to-child transmission rate in HTLV-1/2 infected women attending two public hospitals in the metropolitan area of Rio de Janeiro. PLoS Negl Trop Dis [Internet]. 2019 Jun [cited 2020 Oct 15] ; 13(6):e0007404. Available from: https://doi.org/10.1371/journal.pntd.0007404 https://doi.org/10.1371/journal.pntd.000...
Rio de Janeiro	0,66	1.204	Monteiro et al. 2014¹⁸⁹189. Monteiro DLM, Taquette SR, Sodré Barmpas DB, Rodrigues NCP, Teixeira SAM, Villela LHC, et al. Prevalence of HTLV-1/2 in pregnant women living in the metropolitan area of Rio de Janeiro. PLoS Negl Trop Dis [Internet]. 2014 Sep [cited 2020 Oct 15] ; 8:e3146. Available from: https://doi.org/10.1371/journal.pntd.0003146 https://doi.org/10.1371/journal.pntd.000...
São Paulo	0,1	913	Olbrich Neto et al, 2004¹⁸²182. Olbrich-Neto J, Meira DA. Soroprevalence of HTLV-I/II, HIV, siphylis and toxoplasmosis among pregnant women seen at Botucatu - São Paulo - Brazil: risk factors for HTLV-I/II infection. Rev Soc Bras Med Trop [Internet]. 2004 [cited 2020 Oct 15] ; 37(1):28-32. Available from: https://doi.org/10.1590/S0037-86822004000100008 https://doi.org/10.1590/S0037-8682200400...
Sul
Paraná	0,31	643	Medeiros et al. 2018¹⁵⁹159. Medeiros ACM, Vidal LRR, Von Linsingen R, Ferin AN, Strapasson TB, Almeida SM, et al. Confirmatory molecular method for HTLV-1/2 infection in high-risk pregnant women. J Med Virol [Internet]. 2018 May [cited 2020 Oct 15] ; 90(5):998-1001. Available from: https://doi.org/10.1002/jmv.25014 https://doi.org/10.1002/jmv.25014... ^d

Saúde Pública

Saúde Pública

Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: infección por virus linfotrópico de células T humanas (HTLV)

Resumen

Presentación

Aspectos epidemiológicos

Aspectos clínicos

Mielopatía asociada al HTLV-1

Leucemia/linfoma de células T del adulto

Alteraciones dermatológicas en el individuo con HTLV

Uveítis en el individuo con HTLV-1

Coinfecciones en el individuo con HTLV

Diagnóstico

Tratamiento

Vigilancia, prevención y control

Poblaciones especiales

Gestantes

Poblaciones indígenas

Conclusiones

Agradecimiento

Referencias bibliográficas

Fechas de Publicación

Histórico