Analysis of proviral load levels in HTLV-1 carriers with different neurological impairment conditions




HTLV-1; Tropical Spastic Paraparesis; Neurological disorders; Proviral load.


Objectives: To analyze the levels of proviral load (CPV) in patients with HTLV-1 with different conditions of neurological impairment. Methodology: Cross-sectional study, conducted from March to October 2017, with 43 patients with HTLV-1, divided into three groups in decreasing order of neurological involvement, according to the updated proposal of the clinical diagnosis criteria for HAM / TSP: Defined for HAM / TSP (Group 1, n = 7); Probable / Possible for HAM / TSP (Group 2, n = 9); Without HAM / TSP (Group 3, n = 27). The ANOVA test (one criterion) was used to verify the difference between the groups' mean CPV (p-value≤0.05). Results: The groups presented the following average CPV values: G1 = 9.00 ± 11.18; G2 = 1.88 ± 3.92; G3 = 2.81 ± 4.03 copies / 106 PBMC. In the intergroup comparison, of the difference between the means of CPV, a significant difference was observed between groups 1 and 2 and between groups 1 and 3 (p <0.05); a significantly higher mean of CPV was not observed in the HTLV-1 infected groups with neurological impairment, compared to those infected without neurological impairment (p = 0.7063). Conclusion: CPV in patients with HTLV-1 seems to help the clinical evaluation of neurological impairment in the classification of classic cases of HAM/TSP, but it is not an important indicator of initial clinical conditions of HAM/TSP.


Araujo, A. Q. C., & Wedemann, D. (2019). HTLV-1 Associated Neurological Complex. What is Hidden below the Water? AIDS Reviews. 21,211-217.

Araujo, A. Q. C. (2019) Neurologic complications of HTLV-1: a review. Revista Brasileira de Neurologia. 55(2), 5-10.

Bangham, C. R., Araujo, A., Yamano, Y., & Taylor, G. P. (2015) HTLV-1-associated myelopathy/tropical spastic paraparesis. Nature Reviews Disease Primers. 1:15012.

Batista, E. S., Oliveira, P. D., Primo, J., Varandas, C. M. N., Nunes, A. P., Bittencourt, A.L, et al. (2019) HTLV-1 proviral load in infective dermatite associated with HTLV-1 does not increase after the development of HTLV-1-associated myelopathy/tropical spastic paraparesis and does not decrease after IDH remission. PLOS Neglected Tropical Diseases. 13(12):e0007705.

Carneiro-Proietti, A. B. F., Proietti, F. A., & Catalan-Soares, B. C. (2002) Human T cell Lymphotropic viruses (HTLV/1-2) in South America: Should It Be a Public Health Concern? Journal Biomedic Sciece. 9, 587-95.

Carod-Artal, F. J. (2009) Immunopathogenesis and treatment of the myelopathy associated to the HTLV-I virus. Reviews Neurology, 48,147-155.

Catalan-Soares, B. Carneiro-Proietti, A. B. F., & Proietti, F. A. (2005) Heterogeneous geographic distribution of human T-cell lymphotropic viruses I and II (HTLV-I/II): serological screening prevalence rates in blood donors from large urban areas in Brazil. Cadernos de Saúde Pública, 21 (3):926-993.

Cook, L. B., Cook, M., Elemans, A. G., & Rowan, B. (2013). Asquith HTLV-1: persistence and pathogenesis, Virology. 435, 131-140.

Da Costa, C. A., Furtado, K. C., Ferreira, L. S., Almeida, D. S., Linhares, A. C., Ishak, R., Vallinoto, A. C., Lemos, J. A., Martins, L. C., Ishikawa, E. A., Sousa, R. C., & Sousa, M. S. (2013). Familial transmission of human T-cell lymphotrophic virus: silent dissemination of an emerging but neglected infection. PLOS Neglected Tropical Diseases. 7(6), 1-7.

De Castro-Costa, C. M. et al. (2006). Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). AIDS Research and Human Retroviruses. 22(10), 931-5.

De Thé, G., & Bomford, R. (1993). An HTLV-I vaccine: why, how, for whom?). AIDS Research and Human Retroviruses. 9(5):381-6.

Dehee, A., Cesaire, R., & Desire, N., et al. (2002). Quantificação da carga proviral de HTLV-I por um ensaio de PCR em tempo real TaqMan. Journal of Virological Methods, 102: 37-51.

Edlich, R. F., Hill, L. G., & Williams, F. M. (2003). Global epidemic of human T-cell lymphotrophic virus type-I (HTLV-I): an update. Journal of Long-Term Effects of Medical Implants. 13(2):127-40.

Ferreira, L. S. C., Costa, J. H. G., Costa, C. A., Melo, M. F. C, Andrade, M. L, Martins. L. C. Ishikawa, E. A. Y., & Sousa, M. S. (2010) Soroprevalência do vírus linfotrópico de células T humanas em comunidades ribeirinhas da região nordeste do Estado do Pará, Brasil. Revista Pan-Amazônica de Saúde, v.1, p.103-108.

Garcia, I. F. S., & Hennington, E. A. (2019). HTLV: uma infecção estigmatizante? Caderno de Saúde Pública. 35(11), e00005419. 10.1590/0102-311X00005419.

Gessain, A., & Mahieux, R. (2012). Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects. Revue Neurologique. Paris, 168, 3.

Grassi, M. F. R., Olavarria, V. N., Kruschewsky, R. A., Yamano, Y., Jacobson, S., Taylor, G. P., Martin, F., & Galvão-Castro, B. (2013). Utility of HTLV proviral load quantification in diagnosis of HTLV-1-associated myelopathy requires international standardization. Journal of Clinical Virology. 58(3): 584–586.

Grassi, M. R. F. G., Olavarria, V. N., Kruschewsky, R. A., Mascarenhas, R. E., Dourado, I., Correia, C. L. L., Castro-Costa, C. M., & Galvao-Castro, B. (2011) Human T Cell Lymphotropic Virus Type 1 (HTLV-1) Proviral Load of HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients According to New Diagnostic Criteria of HAM/TSP. Journal of Medical Virology. 83, 1269–1274.

Hashimoto, K. et al. (1998) Quantitative in situ PCR assay of HTLV-1 infected cells in peripheral blood lymphocytes of patients with ATL, HAM/TSP and asymptomatic carriers. Journal of the Neurological Science, Amsterdam, 159, (1)67-72.

Haziot, M. E., Gascon, M. R., Assone, T., Fonseca, L. A. M., Luiz, O. D. C., Smid, J., et al. (2019) Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load. PLOS Neglected Tropical Diseases. 13(5): e0006967.

Jeffery, K., et al. (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of associated myelopathy. Procedings of National Academy of Sciences United States of America, Washington, 96, 3848-3853.

Kaplan, J. E., Osame, M., Kubota, H., et al. (1990) The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. Journal of Acquired Immune Deficiency Syndromes. 3(11): 1096-101.

Koga, Y., Iwanaga, M., Soda, M., Inokuchi, N., Sasaki, D., Hasegawa, H., Yanagihara, K., et al. (2010). Trends in HTLV-1 prevalence and incidence of adult T-cell leukemia/lymphoma in Nagasaki, Japan. Journal of Medical Virology. 82(4):668-74.

Kondo, T., Kono, H., Miyamoto, N., Yoshida, R., Toki, H., Matsumoto, I., Hara, M., et al. (1989) Age- and sex-specific cumulative rate and risk of ATLL for HTLV-I carriers. International Journal of Cancer.15, 43(6):1061-1064.

Kubota, R., et al. (1993) Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy. Journal of Neuroimmunology, Amsterdam, 42, 2,147-154.

Loureiro, P. (2008) Infecção pelo HTLV-1: diagnóstico e determinação da carga proviral em indivíduos assintomáticos e com enfermidades associadas em serviço de referência no Nordeste. Tese (Doutorado em Saúde Pública) - Centro de Pesquisas Aggeu Magalhães Fundação Oswaldo Cruz, Recife-PE.

Maloney, E. M., Cleghorn, F. R., Morgan, O. S., Rodgers-Johnson, P., Cranston, B., Jack, N., Blattner W. A., et al. (1998) Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad. Journal of Acquired Immune Deficiency Syndromes. 1; 17(2):167-70.

Manns, A., Hisada, M., & Grenade, L. L. (1999) Human T-lymphotropic virus type I infection. Lancet, London, 33 (9168): 1951-1958.

Martin, F., Fedina, A., Youshya, S., & Taylor, G. P. (2010). A 15-year prospective longi- tudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK. Journal of Neurology, Neurosurgery and Psychiatry. 81:1336-40.

Montanheiro, P. A., 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 Journal Medical Biological Research, Ribeirão Preto, 38(11), 2005. <>.

Nagai, M., et al. (1998) 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. Journal of Neurovirology, Houndmills, 4, (6):586-593.

Olavarria, V. N. G., et al. (2006) HTLV-1 proviral load in peripheral mononuclear cell quantified in TSP/HAM patients, asymptomatic and oligosymptomatic HTLV-1 carries. In: Simpósio Internacional Sobre Htlv No Brasil, 9, 2006, Belo Horizonte, Temas livres. Uberaba: Sociedade Brasileira de Medicina Tropical, 102.

Oliveira-Filho, A. B., Araújo, A. P. S., Souza, A. P. C., Gomes, C. M., Silva-Oliveira, G. C., Martins, L. C., Fischer, B., Machado, L. F. A., Vallinoto, A. C. R., Ishak, R., Lemos, J. A. R., & Kupek E. (2019). Human T-lymphotropic virus 1 and 2 among people who used illicit drugs in the state of Pará, northern Brazil. Scientific Reports. 14, 9(1), 14750. 10.1038/s41598-019-51383-7.

Osame, M. (1990) Review of WHO Kagoshima meeting and diagnostic guidelines for HAM/TSP. in: Blattner WA. Human Retrovirology: HTLV, New York: Raven, 90; 191-197.

Pereira, A. S., Shitsuka, D. M., Parreira, F. J., & Shitsuka, R. (2018). Metodologia da pesquisa científica. UFSM.

Pineda, M. V., Bouzas, M. B., Remesar, M., Fridman, A., Remondegui, C., Mammana, L., et al. (2019) Relevance of HTLV-1 proviral load in asymptomatic and symptomatic patients living in endemic and non-endemic areas of Argentina. PLoS ONE 14(11): e0225596.

Proietti, F. A., Carneiro-Proietti, A. B., Catalan-Soares, B. C., & Murphy, E. L. (2005) Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 5; 24(39):6058-68.

Schierhout, G., Mcgregor, S., Gessain, A., Einsiedel, L., Martinello, M., & Kaldor, J. (2020). Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet. 20(1),133-143.

Silva, I. C., Pinheiro, B. T., Nobre, A. F. S., Coelho, J. L. P., Pereira, C. C. C., Ferreira, L. S. C., Almeida, C. P. S., Viana, M. N. S. A., Almeida, D. S., Falcão, J. R., Santos, Y. C. V., Araújo, M. W. L., Borges, M. S., Nascimento, L. D., Valentim, L. S., Casseb, J. S. R., Costa, C. A., & Sousa, M. S. (2018). Moderada endemicidade da infecção pelo vírus linfotrópico-T humano na região metropolitana de Belém, Pará, Brasil / Moderate endemicity of the human T-lymphotropic virus infection in the metropolitan region of Belém, Pará, Brazil. Revista Brasileira de Epidemiologia. 21: e180018.

Tanajura, D., Castro, N., Oliveira, P., Neto, A., Muniz, A., Carvalho, N. B., et al. (2015) 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. Clinical Infectious Diseases. 61:49-56.

Vallinoto, A. C., Pontes, G. S., Muto, N. A., Lopes, I. G., Machado, L. F., Azevedo, V. N., et al. (2006). Identification of human T-cell lymphotropic virus infection in a semi isolated Afro-Brazilian quilombo located in the Marajó Island (Pará, Brazil). Memórias do Instituto Oswaldo Cruz. 101 (1):103-105.

Vallinoto, A. C., Muto, N. A., Pontes, G. S., Machado, L. F., Azevedo, V. N., Santos, S. E., et al. (2004). Serological and molecular evidence of HTLV-I infection among Japanese immigrants living in the Amazon region of Brazil. Japanese journal of infectious diseases. 57(4)156-159.



How to Cite

ASSIS, I. M. de .; DOMINGUES , M. M. .; ALMEIDA, D. de S. .; COVRE, L. de S. C. .; LA-ROQUE, D. G. L. de .; SILVA, I. C. .; NOBRE, A. F. S. .; BORGES, M. da S. .; PEREIRA, C. C. C. .; SANTANA, B. B. .; VALLINOTO, A. C. R. .; SOUSA, M. S. de . Analysis of proviral load levels in HTLV-1 carriers with different neurological impairment conditions. Research, Society and Development, [S. l.], v. 10, n. 3, p. e22310313264, 2021. DOI: 10.33448/rsd-v10i3.13264. Disponível em: Acesso em: 12 apr. 2021.



Health Sciences