Serological and virological evaluation of human T-lymphotropic virus type 1 infection in family groups from Tumaco, Colombia / Evaluación serológica y virológica de la infección por el virus linfotrópico de células T humanas de tipo 1 en grupos familiares de Tumaco, Colombia

Introduction: To date there has been no statistical evaluation of the profiles of immunoglobulin classes and viral replication as variables in the study of HTLV-1 infection and circulation among families in virus-endemic areas of Colombia. Objective: To evaluate the correlation of several immunological and molecular characteristics with the transmission and circulation of HTLV-1 among families in the town of Tumaco. Materials and methods: Plasma levels of HTLV-1 specific immunoglobulin classes IgG, IgM and IgA1, as well as IgG and sIgA in oral fluids, were calculated for 32 members of 10 family groups from Tumaco in which the mother and at least one child were infected with the virus. Levels of the different immunoglobulin classes were correlated with viral RNA circulating in plasma or oral fluids and the proviral burden as detected by RT-PCR. Results: Significant differences were determined between mothers and carrier children for immunoglobulin levels (p=0.037) and proviral burden (p=0.002). The overall estimate of IgG in plasma and sIgA in oral fluids could be correlated with the circulation of free viral RNA in both fluids and high proviral burden, and associated with HAM/TSP mothers. The detection of anti- tax IgG in plasma revealed differences between HAM/TSP mothers and their offspring. Conclusion: The study of immunological and molecular variables permitted the analysis of HTLV-1 circulation among families of Tumaco. The strong correlation between levels of IgM specific for the virus and viral RNA circulating in fluids indirectly confirmed the transmission of HTLV-1 among families.

Introducción. Todavía no hay una evaluación estadística de los perfiles de las clases de inmuno- globulina s y la replicación viral, como variables para estudiar la infección y la circulació n del HTLV-1 en familias de zonas endémicas en Colombia. Objetivo. Evaluar la correlación de varias características inmunológicas y moleculares, con la transmisión y circulación del virus en familias del municipio de Tumaco. Materiales y métodos. Se calcularon los niveles de IgG, IgM e IgA1 en plasma, e IgG y IgA secretoria en fluido oral, de 32 miembros de 10 grupos familiares de Tumaco, en los que la madre y, al menos, un hijo estaban infectados con el virus. La concentración de las diferentes clases de inmunoglobulinas se pudo correlacionar con la circulación de ARN viral libre en plasma y fluido oral, y la carga proviral, según su detección mediante reacción en cadena de la polimerasa de transcripción inversa. Resultados. Se encontraron diferencias significativas en los niveles de inmunoglobulinas (p=0,037) y en la carga proviral (p=0,002) entre madres e hijos portadores. La estimación total de IgG en plasma e IgA secretoria en fluido oral, se pudo correlacionar con la circulación de ARN viral libre en ambos fluidos y una alta carga proviral, y se asoció con las madres paraparesia espástica tropical o mielopatía asociada con el HTLV-1. La detección en plasma de IgG anti-Tax reveló diferencias entre ellas y sus hijos. Conclusión. El estudio de las variables inmunológicas y moleculares permitió analizar la circulación del HTLV-1 en familias de Tumaco. La fuerte asociación entre los niveles de IgM específica para el virus y el ARN viral circulante en los fluidos y la carga proviral, confirmó indirectamente la transmisión intrafamiliar del virus.

Difficulties in HAM/TSP diagnosis / Dificuldades no diagnóstico da HAM/TSP

The World Health Organization recommends the use of Osame's criterion (1990) for the diagnosis of HTLV-I-associated myelopathy (HAM/TSP). In 2006, a group of neurologists developed a Brazilian criterion that can diagnose HAM/TSP from its onset. OBJECTIVE: It was to test the agreement between both criteria. METHODS: The study included evaluation of clinical and laboratory findings of 35 patients. The ELISA, Western blot and/or polymerase chain reaction was used to search for anti-HTLV-I antibodies. The analysis of agreement was based on the calculation of Kappa. RESULTS: Concordance of 100% (Kappa=1) occurred in cases of "defined" HAM/TSP, but not in patients with "probable" diagnosis. CONCLUSION: The Brazilian criteria was as effective as Osame's criteria for the diagnosis of "defined" HAM/TSP. However, both require more specific biological markers in cerebrospinal fluid for the laboratory diagnosis of probable cases.

A Organização Mundial da Saúde recomenda o uso do critério de Osame (1990) para o diagnóstico da mielopatia associada ao vírus HTLV-I (HAM/TSP). Em 2006, um grupo de neurologistas elaborou um critério brasileiro capaz de diagnosticar HAM/TSP desde suas manifestações iniciais. OBJETIVO: Foi testar a concordância entre ambos os critérios. MÉTODOS: O estudo incluiu a avaliação dos achados clínicos e laboratoriais de 35 pacientes. Os métodos de ELISA, Western blot e/ou reação em cadeia da polimerase foram utilizados para pesquisa de anticorpos anti-HTLV-I. A análise da concordância baseou-se no cálculo do índice Kappa. RESULTADOS: Concordância de 100% (índice Kappa=1) ocorreu nos casos de HAM/TSP "definida", mas não nos pacientes com o diagnóstico "provável". CONCLUSÃO: O critério brasileiro foi tão eficaz quanto o critério de Osame para o diagnóstico de HAM/TSP "definido". No entanto, ambos necessitam de marcadores biológicos mais específicos no líquido cefalorraquidiano para o diagnóstico laboratorial dos casos prováveis.

Diagnóstico laboratorial da mielopatia associada ao HTLV-I: métodos para análise do líquido cefalorraquidiano / Laboratorial diagnosis of HTLV-I associated myelopathy: methods for the cerebrospinal fluid analysis

O vírus linfotrópico de células T humanas do tipo I (HTLV-I) pode causar uma doença neurológica inflamatória, crônica e incapacitante, que acomete a medula espinhal, denominada mielopatia associada ao HTLV-I/paraparesia espástica tropical (PET/MAH). A verificação de anticorpos da classe G (IgG) anti-HTLV-I no soro e no líquido cefalorraquidiano (LCR) representa importante parâmetro para o diagnóstico laboratorial da PET/MAH. OBJETIVO: Avaliação crítica dos métodos utilizados para verificação da presença e da produção intratecal de anticorpos totais e anti-HTLV-I no LCR para o diagnóstico de PET/MAH. MÉTODO: Realizou-se uma revisão sistemática de artigos da literatura médica, usando-se palavras-chave da língua inglesa como cerebrospinal fluid, intrathecal synthesis of antibodies, HTLV-I, HAM/TSP. As bases de dados utilizadas incluíram Pubmed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), MEDlars onLINE (Medline) e Cochrane Library. RESULTADO: Foram selecionados 14 artigos: cinco relacionados com a presença do anticorpo IgG específico no LCR; nove sobre síntese intratecal de anticorpos totais (IgG ou IgG/IgA/IgM) e específicos anti-HTLV-I (IgG ou IgM). DISCUSSÃO: O estudo isolado da presença de anticorpo IgG anti-HTLV-I no LCR não discrimina a fração produzida no sistema nervoso central (SNC), possui baixa especificidade (40 por cento) para o diagnóstico de PET/MAH. A demonstração da síntese intratecal de anticorpos IgG anti-HTLV-I possui maior relevância por suas elevadas especificidade (89 por cento) e sensibilidade (83 por cento). Entre os métodos para a avaliação da síntese intratecal de anticorpo específico, destaca-se o índice de IgG anti-HTLV-I, segundo Reiber e Felgenhauer(18), o qual se baseia no teste do ensaio imunossorvente ligado à enzima (ELISA), com análise simultânea do LCR e do soro. Outros estudos utilizam pequenas amostragens e não demonstram sensibilidade e especificidade no teste do LCR...

The human T-cell lymphotropic virus type I (HTLV-I) may cause HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), an incapacitating chronic inflammatory disease of the spinal cord. The detection of IgG anti-HTLV-I antibodies in the serum and cerebrospinal fluid (CSF) has been an important parameter for the laboratorial diagnosis of HAM/TSP. OBJECTIVE: critical evaluation of the methods applied to detect the presence and intrathecal production of total antibodies and anti-HTLV-I in the CSF for the diagnosis of HAM/TSP. METHODS: We performed a systematic review of medical articles by using the key words: "cerebrospinal fluid, intrathecal synthesis of antibodies, HTLV-I associated myelopathy, HTLV-I, HAM/TSP". The used databases included: PubMed, Lilacs, Medline and Cochrane Library. RESULTS: A total of 14 articles were selected: five studies were related to the presence of specific IgG antibody in the CSF and nine studied the intrathecal synthesis of total antibodies (IgG or IgG/IgA/IgM) and specific anti-HTLV-I (IgG or IgM). DISCUSSION: The isolated study of the presence of IgG antibody anti-HTLV-I in the CSF does not show the fraction produced in the central nervous system, which represents low specificity (40 percent) for the diagnosis of HAM/TSP. The demonstration of the intrathecal synthesis of IgG anti-HTLV-I antibodies is more relevant due to its high specificity (89 percent) and sensibility (83 percent). According to Reiber & Felgenhauer (1987), the index IgG anti-HTLV-I, which is based on ELISA test with simultaneous CSF and serum analysis, stands out from the other methods applied to evaluate the intrathecal synthesis of specific antibody. Other studies use small samples and do not demonstrate the sensibility and specificity of the test in the CSF. Only one study shows statistical analysis. CONCLUSION: The immunological diagnosis of the CSF in HAM/TSP requires the standardization of methods, which should be based...

Lack of HTLV-I carriers in the Sami, an ethnic group living in the Arctic area in Norway.

The Sami is an ethnic group with ill-defined genetic origins, living in the northern areas of the Scandinavian Peninsula and Russia. Distinct from other European populations in culture and language, they are generally deemed to be remote from the Caucasian lineage. In order to ascertain whether the Sami are genetically linked to Asiatic Mongoloids, we investigated serological markers of human T-cell leukemia virus type I (HTLV-I) infection. Particle agglutination tests for serum HTLV-I antibody were performed for 400 Sami living in Finnmark, the northernmost county of Norway, and in 380 Caucasians (or Norse) in the same region, using serum samples collected for the purpose of studying cardiovascular disease among Northland people in 1974-75. One sample from a Sami showed a tentatively positive reaction, and 4 sera from Sami and 4 from Norse individuals exhibited non-specific agglutination. However, none of the 9 sera showed a positive result in western blotting for HTLV-I proteins, namely, gp46, p53, p24, and p19. Since HTLV-I is distributed most prevalently among northern and southwestern Japanese in Asia and Andeans in South America, the absence of HTLV-I in the Sami might suggest their genetic remoteness from these ethnic groups.

Evaluación de una técnica de enzimoinmunoensayo para detección de anticuerpos anti-HTLV-I / Anti HTLV-EIA screening test assessment

El HTLV-I y el HTLV-II son virus cuya transmisión ocurre de madre a hijo, por contacto sexual y por transfusiones de sangre o por compartir agujas contaminadas. El HTLV-I está asociado al menos con dos enfermedades, la leucemia-linfoma T del adulto y la parapesia espástica tropical. Con el fin de prevenir la transmisión por vía transfusional en varios países se testean las donaciones de sangre para Ac anti-HTLV-I. El presente estudio tuvo como objetivo la evaluación de un nuevo test de enzimoinmunoensayo para detección de Ac anti HTLV-I (Abbott HTLV-I 2.0 EIA, USA) utilizando muestras repetidamente reactivas por la prueba de AP y positivas, indeterminadas o negativas por WB. Se utilizaron 63 sueros obtenidos de donantes voluntarios vinculares de sangre. Treinta fueron negativos por WB, 13 reactivos para HTLV-I, 2 reactivos para HTLV-II, uno para HTLV-I/II y 17 indeterminados. Todas las muestras positivas por WB también lo fueron por EIE; en cuanto a las negativas por la técnica confirmatoria, el 13 por ciento fue reactivo por EIE. Por último, de los sueros indeterminados, el 53 por ciento fue positivo por EIE. La técnica del EIE resultó tener muy buena sensibilidad y podría constituir una alternativa útil en el caso de no disponer momentáneamente de reactivos para realizar la confirmación. Según lo observado en nuestra experiencia, un resultado positivo por EIE para una muestra repetidamente reactiva por AP indica con alta probabilidad que están presentes Ac anti-HTLV y viceversa.

HTLV-I/II as a common etiology of myelopathies in Bahia, Brazil

Infection by human T-cell lymphotrophic virus type I (HTLV-I) is associated with a myelopathy known as tropical spastic paraparesis (TSP). The prevalence of HTLV-I infection was found to be high in a pilot study in Bahia, Brazil. In the present study, among patients with myleopathy of unclear etiology, 27 per cent (17/62) were immunoblot reactive to HTLV-I/II (serum and CSF), but none of 40 consecutive patients seen at the neurological clinic and having a well-established neurological diagnosis had detectable antibodies against those viruses (discrimination between HTLV-I and HTLV-II was not possible with the tests we used). The clinical syndrome of typical TSP with upper limb hyperreflexia was found to be a significant feature among the HTLV-I/II-seropositive patients compared to seronegative individuals. The 17 HTLV-I/II-reactive individuals had negative tests for syphilis, toxoplasmosis and schistosomiasis. TSP was also associated with female gender (P=0.001). We conclude that TSP is strongly associated with HTLV-I/II infection in women in Bahia.

Preliminary survey of anti-HTLV-I in northeastern-Thais.

The anti-HTLV-I prevalence was studied by particle agglutination technique (PA) in 2,609 samples including: 403 antenatal care women from Srinagarind Hospital, Faculty of Medicine, 342 high-risk sexually transmitted disease blood donors and 1,864 randomly selected blood donors from the Blood Transfusion Centre, Faculty of Medicine, Khon Kaen University. All of the 2,609 samples gave negative anti-HTLV-I. The result revealed that HTLV-I infection is not common in northeast-Thailand. However, as the sample size from this study may be too small, further study should be carried out.

Evaluation of HTLV-I/II infection in blood donors in Buenos Aires

HTLV-I and HTLV-II are two related retroviruses that are transmitted by sexual contact, breast feeding, blood transfusion and needle sharing. In this study the prevalence of HTLV-I and HTLV-II was evaluated in voluntary blood donors as a measure of the infection in the general population. Samples were tested by a gelatine particle agglutination test and repeatedly reactive samples were confirmed by Western blot tests (WBT), enriched with recombinant rgp21, rgp46I y rgp46II proteins, which differentiates HTLV-I and HTLV-II antibodies. Of 19,426 samples, 40 were repeatedly reactive by particle agglutination (0.21 percent). When analyzed by WBT, 6 met the criteria for HTLV-I (0.036 percent), 2 for HTLV-II (0.01 percent) and 1 for HTLV-I/II, 13 samples were indeterminate and 18 were negative. The prevalence is low and comparable to that from non endemic countries. Screening for anti HTLV-I/II antibodies is necessary to prevent transmission through blood transfusions.

Anticuerpos anti-virus linfotrópicos de células T humanas en sujetos de alto riesgo para la infección por VIH en Monterrey / Anti-HTLV-1/2 antibodies in a population of high risk for HIV infection in Monterrey, Mexico

El VIH es el agente etiológico del síndrome de la inmunodeficiencia adquirida o SIDA y el HTLV-1 se ha asociado a la leucemia/linfoma de las células T de adultos y a la paraparesis espástica tropical. En México existe poca información sobre la incidencia de la infección por HTLV-1. En el presente trabajo buscamos la presencia de anticuerpos dirigidos contra HTLV-1 en 100 sueros de pacientes de alto riesgo para la infección por VIH, del área de Monterrey, N. L. En 93 sueros se detectaron anticuerpos anti VIH y dos dieron resultados indeterminados por inmunoelectrotransferencia. Tres sueros VIH positivos dieron también positiva la prueba de aglutinación para HTLV-1; sin embargo, en la prueba confirmatoria de inmunoelectrotransferencia, las tres muestras resultaron negativas para HTLV-1

Antibody to human T-lymphotropic virus in a patient with Guillain-Barre syndrome: case report

Amostra de soro obtida de paciente com a sindrome de Guillain-Barre revelou-se positiva quanto a presenca de anticorpos para o virus linfotropico humano T (HTLV-I) pelo metodo imuno-enzimatico (ELISA) e a analise por "Western-Blot". Resultaram negativos os testes visando a deteccao de enterovirus (incluindo poliovirus) a partir de material fecal, tanto em cultura de tecidos como em camundongos recem-nascidos; exames com amostras de soro aguda e convalescente nao exibiram qualquer evidencia de infeccao recente pelos tres tipos de poliovirus. O teste de Paul-Bunnel, assim como o "ELISA" para a deteccao de IgM anti-citomegalovirus resultaram negativos. Nao foi registrada, no presente caso, quer a leucemia adulta de celulas T, quer linfomas.

A case of HTLV-I associated myelopathy(HAM) in Korea

We report the first Korean case of HTLV-I associated myelopathy (HAM), which was confirmed by Western blot assay of serum and cerebrospinal fluid. Interestingly, the proband's wife was a Japanese Korean who had lived in the endemic area of HAM, Kyushu. Japan, Investigations revealed significantly elevated anti HTLV-I antibody titers in the serum, but not in the CSF, suggesting that she was a carrier of HTLV-I. Considering that the patient had not had a previous blood transfusion, the most common route of HTLV-I, it is likely that the patient was infected by his wife through sexual intercourse. Although previous reports suggest that the transmission of HTLV-I is essentially from man to man or man to woman, our case suggests that woman to man transmission also occurs.

HTLV-1 antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil

Foi pesquisada a presença de HTLV-1 anticorpos no soro e no LCR de 150 pacientes com afecçöes do sistema nervoso, particularmente mielopatias. Os pacientes foram considerados segundo três grupos, de acordo com a possível relaçäo entre a doença e a presença de HTLV-1 anticorpos: sem risco de relaçäo (grupo controle); grupo de risco ocasional; grupo de risco possível. Este último abrange 56 pacientes com paraparesia ou paraplegia crural espástica de etiologia näo esclarecida (PE). Foi utilizada para a pesquisa a técnica de aglutinaçäo passiva de partículas para anti-ATLA anticorpo, sendo obtidos os seguintes resultados: näo foram detectados HTLV-1 anticorpos no grupo controle e foram detectados (soro e/ou LCR) em 16,5% dos pacientes do segundo grupo e em 55,4% daqueles do terceiro grupo. O quadro clínico dos pacientes com PE e HTLV-1 anticorpos era compatível a paraparesia espática tropical (PET). Foi verificada diferença significativa quanto a dados do exame de LCR (citologia, concentraçäo proteica e teor de globulinas gama) ao se compararem os pacientes com PET com HTLV-1 anticorpos no LCR àqueles com PE em que tais anticorpos näo foram detectados nem no soro e nem no LCR. Os resultados deste estudo confirmam a elevada incidência da PET no Brasil e ilustram a necessidade da pesquisa desses anticorpos também no LCR

Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report)

Forty-tree (31.4%) out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (Elisa). Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0%) or the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2%) out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7%) out of 30 Elisa positive specimens were also shown to be positive by either Western blot analysis (WB) or indirect immunogold electron microscopy (IIG-EM)