Leucemia/linfoma T del adulto tipo linfomatoso por HTLV-1 en una mujer joven / Adult T cell lymphoblastic leukemia/lymphoma by HTLV-1 in a young woman

Resumen La leucemia/linfoma T del adulto (LLTA) de tipo linfomatoso es un subtipo del linfoma de las células T, causado por la infección del virus linfotrópico de células T humanas tipo 1 (HTLV-1); el cual genera una integración proviral en el ADN del hospedero y expansión clonal de linfocitos T. Presentamos el caso de una mujer de 20 años que desarrolló linfadenopatías múltiples, hepatoesplenomegalia y fiebre, con serología positiva para HTLV-1 y reacción de polimerasa en cadena (RPC) con la integración proviral en el ADN del hospedero. La inmunohistoquímica en un ganglio linfático fue positiva para células T CD4+ y CD8+. La LLTA ha sido descrito en todas las áreas endémicas del HTLV-1; sin embargo, existen diferencias en la edad de presentación según la región: 40 a 50 años en América del Sur y 60 años en Japón. Presentamos uno de los pocos casos reportados de LLTA de tipo linfomatoso en adultos jóvenes.

Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.

Evaluation of the cervicovaginal environment in asymptomatic Human T-cell lymphotropic virus type 1 infected women

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.

Hepatitis C viral load in HCV-monoinfected and HCV/HIV-1-, HCV/HTLV-1/-2-, and HCV/HIV/HTLV-1/-2-co-infected patients from São Paulo, Brazil

ABSTRACT Co-infections of hepatitis C virus (HCV) and either human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type 1 (HTLV-1) or type 2 (HTLV-2) have been described as having an impact on HCV viremia and subsequent disease progression. HCV load in serum samples from 622 patients (343 males, 279 females; median age 50.8 years) from São Paulo/southeast Brazil was analyzed using the Abbott Real Time HCV assay (Abbott Molecular Inc., IL, USA). Samples were obtained from HCV-monoinfected (n = 548), HCV/HIV-1- (n = 41), HCV/HTLV-1- (n = 16), HCV/HTLV-2- (n = 8), HCV/HIV/HTLV-1- (n = 4), and HCV/HIV/HTLV-2-co-infected (n = 5) patients, and results were compared among the groups and according to sex. The median HCV load in HCV-monoinfected patients was 5.23 log10 IU/mL and 0.31 log10 higher in men than in women. Increases in viral load of 0.51 log10, 0.54 log10, and 1.43 log10 IU/mL were detected in HCV/HIV-1-, HCV/HTLV-1- and HCV/HIV/HTLV-1-co-infected individuals, respectively, compared with HCV-monoinfected counterparts. In contrast, compared to HCV/HIV co-infected patients, HCV/HTLV-2-co-infected patients had an HCV load of 5.0 log10 IU/mL, whereas HCV/HIV/HTLV-2-co-infected patients had a median load 0.37 log10 IU/mL lower. Significant differences in HCV loads were detected, with males and HCV/HIV-1- and HCV/HIV/HTLV-1-co-infected patients presenting the highest values. Conversely, females and HCV/HTLV-2-co-infected patients exhibited lower HCV loads. Overall, HCV viremia is increased in HIV and/or HTLV-1-co-infection and decreased in HTLV-2 co-infection.

HUMAN T-LYMPHOTROPIC VIRUS 1 (HTLV-1) AND HUMAN T-LYMPHOTROPIC VIRUS 2 (HTLV-2): GEOGRAPHICAL RESEARCH TRENDS AND COLLABORATION NETWORKS (1989-2012)

Publications are often used as a measure of research work success. Human T-lymphotropic virus (HTLV) type 1 and 2 are human retroviruses, which were discovered in the early 1980s, and it is estimated that 15-20 million people are infected worldwide. This article describes a bibliometric review and a coauthorship network analysis of literature on HTLV indexed in PubMed in a 24-year period. A total of 7,564 documents were retrieved, showing a decrease in the number of documents from 1996 to 2007. HTLV manuscripts were published in 1,074 journals. Japan and USA were the countries with the highest contribution in this field (61%) followed by France (8%). Production ranking changed when the number of publications was normalized by population (Dominican Republic and Japan), by gross domestic product (Guinea-Bissau and Gambia), and by gross national income per capita (Brazil and Japan). The present study has shed light on some of the defining features of scientific collaboration performed by HTLV research community, such as the existence of core researchers responsible for articulating the development of research in the area, facilitating wider collaborative relationships and the integration of new authors in the research groups.

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.

Inferences about the global scenario of human T-cell lymphotropic virus type 1 infection using data mining of viral sequences

Human T-cell lymphotropic virus type 1 (HTLV-1) is mainly associated with two diseases: tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and adult T-cell leukaemia/lymphoma. This retrovirus infects five-10 million individuals throughout the world. Previously, we developed a database that annotates sequence data from GenBank and the present study aimed to describe the clinical, molecular and epidemiological scenarios of HTLV-1 infection through the stored sequences in this database. A total of 2,545 registered complete and partial sequences of HTLV-1 were collected and 1,967 (77.3%) of those sequences represented unique isolates. Among these isolates, 93% contained geographic origin information and only 39% were related to any clinical status. A total of 1,091 sequences contained information about the geographic origin and viral subtype and 93% of these sequences were identified as subtype “a”. Ethnicity data are very scarce. Regarding clinical status data, 29% of the sequences were generated from TSP/HAM and 67.8% from healthy carrier individuals. Although the data mining enabled some inferences about specific aspects of HTLV-1 infection to be made, due to the relative scarcity of data of available sequences, it was not possible to delineate a global scenario of HTLV-1 infection.

Lack of evidence for human infection with Xenotropic murine leukemia virus-related virus in the Brazilian Amazon basin

Introduction This study confirmed the absence of natural infection with Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in human populations of the Brazilian Amazon basin. We demonstrated that 803 individuals of both sexes, who were residents of Belem in the Brazilian State of Pará, were not infected with XMRV. Methods Individuals were divided into 4 subgroups: healthy individuals, individuals infected with human immunodeficiency virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus, types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was investigated by nested PCR to detect the viral gag gene and by quantitative PCR to detect pol. Results There was no amplification of either gag or pol segments from XRMV in any of the samples examined. Conclusions This study supports the conclusions of the studies that eventually led to the retraction of the original study reporting the association between XMRV and human diseases. .

Búsqueda del ADN del virus HTLV-1 en biopsias de pacientes con linfoma cutáneo de células T / Detection of HTLV-1 DNA in biopsies of Chilean patients with cutaneous T-cell lymphoma

Background: Human T-lymphotropic virus-1 (HTLV-1) infection has been associated with the pathogenesis of cutaneous T cell lymphomas (CTCL). Aim: To search for HTLV-1 DNA in skin biopsies of patients with CTCL. Material and Methods: A retrospective study was conducted using 25 biopsies of patients with CTCL. DNA was extracted from lymphoid tissue by microdissection. A nested PCR was conducted to detect HTLV-1 genome using primers for the tax region. As negative controls, four cases of superficial perivascular dermatitis were chosen. As positive controls, five cases of T-cell leukemia/lymphoma (ATCL) were studied. Results: A positive reaction was found in 3 of 25 cases. These biopsies corresponded to a case of Mycosis Fungoides, a case of CD30 (-) T-cell lymphoma and a case of lymphomatoid papulosis. Search was negative in the four cases of superficial perivascular dermatitis and positive in four cases of adult T-cell leukemia/lymphoma (ATCL). Conclusions: HTLV-1 DNA search in tissues is a useful tool recommended to study T-cell lymphomas. HTLV-1 infection only occurs in sporadic cases but may contribute to tumor aggressiveness and prognosis.

The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy

Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

Evolution of HTLV-1 proviral load in patients from Salvador, Brazil

INTRODUCTION: Variations in human T cell lymphotropic virus type 1 (HTLV-1) proviral load (PVL) in infected individuals over time are not well understood. Objective: To evaluate the evolution of proviral load in asymptomatic individuals and HAM/TSP patients in order to help determine periodicity for measuring proviral load. METHODS: A group of 104 HTLV-1 infected patients, followed at the HTLV reference center in Salvador, Brazil, were included in the study (70 asymptomatic and 34 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients). HTLV-1 PVL was measured using real-time polymerase chain reaction (PCR) at baseline and again at another point, either < 12 months, between 12-24 months, or > 24 months. RESULTS: HAM/TSP patients had higher PVL (ranging from 11,041 to 317,009 copies/10(6) PBMC) when compared to asymptomatic individuals (ranging from 0 to 68,228 copies/10(6) PBMC). No statistically significant differences were observed in the medians of PVL in HAM/TSP patients or asymptomatic individuals over time. However, in asymptomatic individuals with a PVL below 50,000 copies/10(6) PBMC, a statistically significant two-fold increase was observed over time. CONCLUSION: HTLV-1-PVL remained stable in both asymptomatic individuals and HAM/TSP patients over time. Frequent monitoring of asymptomatic individuals with low PVLs is recommended and further studies should be conducted to assess the course of PVL in these patients over extended periods of time.

O vírus linfotrópico de células T humanos tipo 1 (HTLV-1): quando suspeitar da infecção?: [revisão] / Human T cell lymphotropic virus (HTLV)1: when should infection be suspected?: [review]

A infecção pelo vírus linfotrópico de células T humanas (HTLV) ocorre há milhares de anos. No entanto, o conhecimento sobre a sua patogênese é recente. Esse vírus é endêmico em várias regiões do mundo. No Brasil encontra-se presente em todos os estados, com prevalências variadas, sendo estimado cerca de 2,5 milhões de infectados. Fatores genéticos e imunológicos do hospedeiro são os principais responsáveis pelas manifestações clínicas associadas, que podem ser divididas em três categorias: neoplásicas, inflamatórias e infecciosas. Destacam-se a mielopatia associada ao HTLV (HAM/TSP) e a leucemia/linfoma de células T do adulto (ATLL) como as primeiras doenças associadas a esse retrovírus. Posteriormente, inúmeras outras doenças têm sido correlacionadas a esse vírus. Esta revisão atualiza conhecimentos epidemiológicos, fisiopatológicos, terapêuticos e principalmente diagnósticos do HTLV. O objetivo é permitir a suspeita etiológica do HTLV em suas diversas manifestações clínicas, hoje pouco correlacionadas com este agente.

Human T Lymphotropic Virus (HTLV) infection has occurred for thousands of years. However, knowledge about this pathogenesis is recent. This virus is endemic worldwide. In Brazil it is present throughout the country , with different prevalence and about 2 5 million infected. Genetic and immunologic characteristics of the host are chiefly responsible for clinically associated manifestations which may be: neoplasic, inflammatory and infectious diseases. HTLV associated myelopathy (TSP/ HAM) and adult T cell leukemia/lymphoma (ATL) stand out as the first diseases associated to this retrovirus. Further, several diseases have been correlated to this virus. This review updates epidemiologic, physiopathologic, therapeutic and diagnostic knowledge of HTLV. The purose is to orient suspicion of HTLV etiology and several clinically associated manifestations, which currenty are seldom correlated with this virus.

Onset of opportunistic infections in patients co-infected by HTLV-1 and HIV-1, with high CD4+ cells count

We reported two cases of patients with coinfection by human immunodeficiency virus (HIV) type 1 and human T-cell lymphotropic virus (HTLV) type I who developed opportunistic infections despite of relatively high CD4+ cells count. These cases showed clinical evidence to consider an earlier antiretroviral treatment for coinfected patientes regardless CD4+ cells counts.

Prevalência, fatores de risco e caracterização genética dos vírus linfotrópico de células T humana tipo 1 e 2 em pacientes infectados pelo vírus da imunodeficiência humana tipo 1 nas Cidades de Ribeirão Preto e São Paulo / Prevalence, risk factors and genetic characterization of human T-cell lymphotropic virus types 1 and 2 in patients infected with human immunodeficiency virus type 1 in the cities of Ribeirão Preto and São Paulo

O objetivo deste estudo foi definir a prevalência dos vírus linfotrópico de células T humana tipo 1 e 2 em pacientes positivos para o vírus da imunodeficiência humana tipo 1 no Estado de São Paulo, Brasil. Avaliamos 319 indivíduos atendidos em clínicas de Ribeirão Preto e Capital. Os pacientes foram entrevistados e testados sorologicamente. Foram seqüenciadas as regiões tax e long terminal repeat para diferenciação e determinação do subtipo. A soroprevalência geral foi de 7,5 por cento (24/319) e esteve associada somente com uso de drogas injetáveis e ao vírus da hepatite tipo C (p<0, 001). O genoma viral foi detectado em 13 das 24 amostras, sendo 12 caracterizadas como HTLV-2 subtipo 2c e uma como 1a. Nossos dados mostraram que o uso de drogas injetáveis é um importante fator de risco para a transmissão de HTLV-2 em populações infectadas pelo vírus da imunodeficiência humana tipo 1.

The aim of this study was to define the prevalence of human T cell lymphotropic virus types 1 and 2 in patients who were positive for human immunodeficiency virus type 1 in the State of São Paulo, Brazil. We evaluated 319 individuals infected with HIV type 1 who were attended at specialized clinics in two cities (Ribeirão Preto and São Paulo). The patients were interviewed and tested for antibodies against HTLV types 1 and 2 (Orthoâ HTLV-1/HTLV-2 Ab-Capture enzyme immunoassay). Direct DNA sequencing of polymerase chain reaction products from the tax region of HTLV type 2 and the long terminal repeat region of HTLV types 1 and 2 were performed to differentiate and determine the subtypes. The overall prevalence of anti-HTLV type 1 and 2 antibodies was 7.5 percent (24/319; 95 percent CI: 5.2-11.5). HTLV type 1 and 2 infection was associated with a history of injected drug use and with antibodies for hepatitis C virus (p < 0.001), but not with age (p = 0.2), sex (p = 0.9), sexual behavior or serological markers for sexually transmitted diseases (anti-Treponema pallidum, anti-human herpesvirus type 8 or anti-hepatitis B virus antibodies) (p > 0.05). HTLV DNA was detected in 13 out of 24 samples, of which 12 were characterized as HTLV subtype 2c and one as HTLV subtype 1a. Among the 12 HTLV type 2 samples, seven were from injected drug users, thus indicating that this route is an important risk factor for HTLV type 2 transmission among our population infected with HIV type 1.

Caracterização molecular do HTLV-1/2 em doadores de sangue em Belém, Estado do Pará: primeira descrição do subtipo HTLV-2b na região Amazônica / Molecular characterization of HTLV-1/2 among blood donors in Belém, State of Pará: first description of HTLV-2b subtype in the Amazon region

Este trabalho objetivou a caracterização molecular do vírus linfotrópico de células T humanas infectando doadores de sangue atendidos na Fundação Centro de Hemoterapia e Hematologia do Pará. Amostras de DNA de 79 indivíduos soropositivos para o vírus linfotrópico de células T humanas foram analisadas por meio da reação em cadeia da polimerase para as regiões genômicas pX, env e 5'LTR, de polimorfismos de comprimento de fragmentos de restrição e do seqüenciamento da região 5LTR, com posterior análise filogenética, definindo o tipo e o subtipo do HTLV circulante na população estudada. Observou-se uma maior prevalência de HTLV-1 (71 por cento) em relação ao HTLV-2 (29 por cento). As amostras de HTLV-1 sequenciadas foram classificadas como pertencentes ao subtipo Cosmopolita, subgrupo Transcontinental, sendo as de HTLV-2 identificadas como HTLV-2c. A análise de polimorfismos de comprimento de fragmentos de restrição da região env e do sequenciamento da região 5'LTR, identificou, pela primeira vez na Amazônia Brasileira, uma amostra de HTLV-2b, enfatizando a necessidade de estudos moleculares contínuos na região para melhor entendimento da epidemiologia de transmissão do HTLV na população e permitir a vigilância epidemiológica da emergência de novos tipos e subtipos.

This study aimed to perform molecular characterization on the human T-cell lymphotropic virus (HTLV) infecting blood donors attended at the Hematology and Hemotherapy Center-Foundation of Pará. DNA samples from 79 HTLV-seropositive individuals were analyzed by means of the polymerase chain reaction on the pX, env and 5'LTR genomic regions; restriction fragment length polymorphism analysis; and sequencing of the 5'LTR region with subsequent phylogenetic analysis. From this, the HTLV types and subtypes circulating in the study population were defined. There was higher prevalence of HTLV-1 (71 percent) than of HTLV-2 (29 percent). HTLV-1 samples were classified as belonging to the Cosmopolitan subtype, Transcontinental subgroup; and the HTLV-2 samples as HTLV-2c. Analysis on the restriction fragment length polymorphisms of the env region and sequencing of the 5'LTR region identified a sample of HTLV-2b, for the first time in the Brazilian Amazon region. This emphasizes the need for ongoing molecular studies in this region, in order to have better understanding of the epidemiology of HTLV transmission in the population, and to enable epidemiological surveillance of the emergence of new types and subtypes.

Polymorphism in the promoter region of the mannose-binding lectin gene among human T-cell lymphotropic virus infected subjects

The present study investigated the frequency of the mutations at positions -550 and -221 of the mannose-binding lectin (MBL) gene in a sample of 75 human T-cell lymphotropic virus (HTLV) infected patients and 96 HTLV seronegative controls, in order to evaluate the occurrence of a possible association between the polymorphism and HTLV infection. A sequence specific primer-polymerase chain reaction was used for discrimination of the polymorphism. The analysis of allele frequencies at position -550 did not show any significant differences between HTLV infected group and controls, but there was a significant difference at position -221. The comparative analysis of haplotypes frequencies were not significant, but the genotype frequencies between the two groups, revealed a higher prevalence of genotype LYLX (25.3 percent), associated with medium and low MBL serum levels among HTLV infected subjects. The odds ratio estimation demonstrated that the presence of genotype LYLX was associated with an increased risk of HTLV infection (p = 0.0096; 1.38 < IC95 percent < 7.7605). There was no association between proviral load and the promoter polymorphism, but when promoter and exon 1 mutations were matched, it was possible to identify a significant higher proviral load among HTLV infected individuals carrying haplotypes correlated to low serum levels of MBL. The present study shows that the polymorphism in the promoter region of the MBL gene may be a genetic marker associated with HTLV infection, and emphasizes the need for further studies to determinate if the present polymorphism have any impact on diseases linked to HTLV infection.

Seroprevalencia de Anticuerpos para Virus Linfotrópicos Humanos (HTLV I/II) en donantes de sangre de una Clínica de Bogotá, Colombia. 1999-2004 / Human T-lymphotropic virus (HTLV I/II) seroprevalence amongst blood-donors in a hospital Bogotá, Colombia,between 1999 and 2004

Objetivo: Determinar la prevalencia de anticuerpos para HTLV I/II, en los donantes de sangre del Banco de Sangre de la Clínica Reina Sofía, ubicada en Bogotá, Colombia. Métodos: Fueron incluidas las muestras de todos los donantes de sangre en el período comprendido entre Abril de 1999 y Agosto de 2004. A estas muestras se les realizó un ELISA para identificación de los virus HTLV I/II; a los donantes con muestras reactivas se les tomó una nueva muestra, la cual se confirmó mediante Western blot (WB). Se analizaron las encuestas de todos los donantes con pruebas reactivas para HTLV I/II en el periodo descrito y se diligenció un formulario con las variables. Resultados: La población total de donantes de sangre estudiados en los cinco años fue de 8 913 donantes, 5 883 (66 por ciento) hombres y 3 030 (34 por ciento) mujeres, con un promedio de 37 años; de los cuales 26 (0,3 por ciento) tuvieron ELISA doblemente reactivo para HTLV I/II y, de estos, solo seis pacientes fueron confirmados mediante WB, los cuales representan una prevalencia de 0,07 por ciento Conclusión: Aunque nuestros hallazgos sugieren una baja seroprevalencia para HTLV I/II, nos permiten resaltar la importancia de implantar la prueba de detección de anticuerpos contra estos virus en todos los Bancos de Sangre del país junto con las demás pruebas que ya son indispensables según la legislación colombiana para poder suministrar sangre y hemocomponentes de calidad.

Objective: This study was aimed at determining anti-human T-lymphotropic virus I/II (HTLV I/II) seroprevalence amongst blood-donors at the Clínica Reina Sofía in Bogotá, Colombia between 1999 and 2004. Methods: All people donating blood at the Clínica Reina Sofía were selected for anti-HTLV I/II testing; a survey was carried out which focused on risk factors. All blood donations were screened by using enzyme immunolinked assay (ELISA); repeatedly reactive serum samples were confirmed as being HTLV I or HTLV II by using Western blot (WB). Results: 8 913 blood donors, 5 883 (66 percent) males and 3,030 (34 percent) females having a mean age of 37 were included in the study; 26 (0,3 percent) were repeatedly reactive in ELISA tests, 6 (0,07 percent) of whom were confirmed by using Western blot (WB). Our findings revealed 0,07 percent HTLV seroprevalence amongst blood-donors, in line with other European and South-American countries. Conclusion: Although our findings suggest low HTLV I/II seroprevalence, blood-donors should be routinely screened to minimise transmission due to occult HTLV I/II infection in Colombia.

Carga proviral do HTLV-1 e HTLV-2: um método simples através da PCR quantitativa em tempo real / HTLV-1 and HTLV-2 proviral load: a simple method using quantitative real-time PCR

Os vírus linfotrópicos de células T humanas, quando integrados ao genoma da célula hospedeira, provírus, têm como marcador de replicação seu DNA proviral. A carga proviral parece ser um importante fator no desenvolvimento de patologias associadas a estes retrovírus. Neste estudo foi desenvolvida uma metodologia para quantificação absoluta da carga proviral dos HTLV-1 e HTLV-2 através da PCR em tempo real. Cinqüenta e três amostras de doadores de sangue com teste de ELISA reagente foram submetidas à metodologia, que utilizou o sistema TaqMan® para três seqüências alvo: HTLV-1, HTLV-2 e albumina. A quantificação proviral absoluta foi determinada através da proporção relativa entre o genoma do HTLV e o genoma da célula hospedeira, levando em consideração o número de leucócitos. O método apresentado é sensível (215 cópias/mL), prático e simples para quantificação proviral, além de eficiente e adequado para confirmação e discriminação da infecção pelos tipos virais.

When the human T cell lymphotropic virus (HTLV) is integrated with the host cell genome (provirus), its proviral DNA is a replication marker. Proviral load appears to be an important factor in the development of diseases related to these retroviruses. In this study, a methodology for absolute quantification of the HTLV-1 and HTLV-2 proviral load using real-time PCR was developed. Fifty-three blood donor samples with positive ELISA test result were subjected to this methodology, which utilized the TaqMan® system for three target sequences: HTLV-1, HTLV-2 and albumin. The absolute proviral load was quantified using the relative ratio between the HTLV genome and the host cell genome, taking into consideration the white blood cell count. The method presented is sensitive (215 copies/ml), practical and simple for proviral quantification, and is efficient and appropriate for confirming and discriminating infections according to viral type.

Resonancia Magnética de médula espinal y cerebro en el correlato clínico de la paraparesia espástica progresiva que se asocia al virus humano linfotrópico tipo-I (HTLV-I) / Brain and spinal cord magnetic resonance imaging in spastic paraparesis associated to human T-lymphotropic virus

Background: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. Aim: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. Material and methods: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Results: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87 percent of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80 percent of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. Conclusions: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis.