HTLV 1/2 Prevalence and risk factors in individuals with HIV/AIDS in Pernambuco, Brazil

Abstract INTRODUCTION: Apart from masking the diagnosis of AIDS in patients with HIV/AIDS, human T-cell lymphotropic virus (HTLV), when present, also increases the risk of myelopathies and neurological disease in these patients. METHODS: Disease prevalence was estimated by ELISA and confirmed by Western blot. RESULTS: The coinfection rate was 1.5% (11/720); 10 of 11 patients had HTLV-1, and the remaining one had HTLV-2. The majority were male, over 40 years old, and of pardo color (ethnicity). CONCLUSIONS: There was no association between the risk factors examined and HTLV/HIV coinfection. This is the first study to report the occurrence of HTLV-2 in Pernambuco.

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)

ABSTRACT The present study evaluated several techniques currently available (commercial kits and in-house assays) for diagnosing human T lymphotropic viruses types 1 and 2 in two groups of patients enrolled at HIV/AIDS specialized care services in São Paulo: Group 1 (G1), n = 1608, 1237 male/371 female, median age 44.3 years old, majority using highly active antiretroviral therapy (HAART); G2, n = 1383, 930 male/453 female, median age of 35.6 years old, majority HAART naïve. Enzyme immunoassays [(EIA) Murex and Gold ELISA] were employed for human T lymphotropic viruses types 1 and 2 screening; Western blotting (WB), INNO-LIA (LIA), real-time PCR pol (qPCR), and nested-PCR-RFLP (tax) were used to confirm infection. Samples were considered human T lymphotropic viruses types 1 and 2 positive when there was reactivity using at least one of the four confirmatory assays. By serological screening, 127/2991 samples were positive or borderline, and human T lymphotropic virus infection was confirmed in 108 samples (three EIA-borderline): 56 human T lymphotropic virus type 1 [G1 (27) + G2 (29)]; 45 human T lymphotropic virus type 2 [G1 (21) + G2 (24)]; one human T lymphotropic virus type 1 + human T lymphotropic virus type 2 (G2); six human T lymphotropic virus [G1 (2) + G2 (4)]. Although there were differences in group characteristics, human T lymphotropic viruses types 1 and 2 prevalence was similar [3.1% (G1) and 4.2% (G2), p = 0.113]. The overall sensitivities of LIA, WB, qPCR, and PCR-RFLP were 97.2%, 82.4%, 68.9%, and 68.4%, respectively, with some differences among groups, likely due to the stage of human T lymphotropic virus infection and/or HAART duration. Indeterminate immunoblotting results were detected in G2, possibly due to the seroconversion period. Negative results in molecular assays could be explained by the use of HAART, the occurrence of defective provirus and/or the low circulating proviral load. In conclusion, when determining the human T lymphotropic virus infection, the findings highlight that there is a need to consider the blood samples with borderline results in screening assays. Of all the tested assays, LIA was the assay of choice for detecting human T lymphotropic virus type 1 and human T lymphotropic virus type 2 in human immunodeficiency virus type 1-infected patients.

Coinfection by HTLV-I/II is associated with an increased risk of strongyloidiasis and delay in starting antiretroviral therapy for AIDS patients

OBJECTIVE: To compare the clinical characteristics and outcomes of HIV-1-HTLV-1 coinfected patients, in Bahia, Brazil. METHODS: Retrospective, comparative study. RESULTS: Among a total of 123 consecutive HIV infected patients, 20 men (20.6 percent) and 6 women (23.1 percent) had detectable antibodies against HTLV-I/II. The major risk factor associated with coinfection by HTLV was intravenous drug use (57.7 percent of coinfected patient versus 9.2 percent of HTLV seronegative patients, p < 0.0001). Coinfected patients had higher absolute lymphocyte counts (1,921 + 762 versus 1,587 + 951, p = 0.03). Both groups of patients had similar means of CD4+ and CD8+ cell counts. However, among patients with AIDS CD4+ cell counts were significantly higher among those coinfected with HTLV-I/II (292 ± 92 cells/mm³, versus 140 ± 177cells/mm³, p = 0.36). The frequency and type of opportunistic infections were similar for both groups, but strongyloidiasis and encephalopathy were more frequently diagnosed in coinfected patients (p < 0.05). On the other hand, patients coinfected with HTLV-I/II received significantly less antiretroviral therapy than singly infected by HIV-1. CONCLUSION: Coinfection by HTLV-I/II is associated with an increased risk of strongyloidiasis for HIV patients. Higher CD4 count may lead to underestimation of immunodeficiency, and delay to initiate antiretroviral therapy.

Hepatitis C virus and human T-lymphotropic virus coinfection: epidemiological, clinical, laboratory and histopathological features / Coinfecção vírus da hepatite C-vírus linfotrópico de células T humanas: aspectos epidemiológicos, clínicos, laboratoriais e histopatológicos

Twenty-four hepatitis C virus patients coinfected with human T-lymphotropic virus type 1 were compared with six coinfected with HTLV-2 and 55 with HCV alone, regarding clinical, epidemiological, laboratory and histopathological data. Fischer's discriminant analysis was applied to define functions capable of differentiating between the study groups (HCV, HCV/HTLV-1 and HCV/HTLV-2). The discriminant accuracy was evaluated by cross-validation. Alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with intravenous drug users were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported abdominal pain or a sexual partner with hepatitis. Coinfected patients presented higher platelet counts, but aminotransferase and gamma-glutamyl transpeptidase levels were higher among HCV-infected subjects. No significant difference between the groups was seen regarding liver histopathological findings. Through discriminant analysis, classification functions were defined, including sex, age group, intravenous drug use and sexual partner with hepatitis. Cross-validation revealed high discriminant accuracy for the HCV group.

Compararam-se 24 pacientes coinfectados pelos vírus da hepatite C/vírus linfotrópico de células T humanas do tipo 1 com 6 coinfectados por VHC/HTLV-2 e 55 infectados pelo VHC, no tocante a dados clínico-epidemiológicos, laboratoriais e histopatológicos. A análise discriminante de Fischer foi utilizada para definir funções capazes de diferenciar os grupos de estudo (VHC, VHC/HTLV-1 e VHC/HTLV-2). A acurácia discriminatória foi avaliada pelo por validação cruzada. O uso de álcool, drogas endovenosas, cocaína inalatória e a parceria sexual com UDEV foram mais freqüentes no grupo VHC/HTLV-2, enquanto queixa de dor abdominal e parceiro sexual com hepatite predominaram no grupo VHC. Os coinfectados apresentaram número maior de plaquetas, enquanto as aminotransferases e a gamaglutamiltranspeptidase foram mais altas no grupo VHC. Não houve diferença entre os grupos à análise histopatológica do fígado. Por análise discriminante definiram-se funções classificatórias, incluindo as variáveis sexo, faixa etária, uso de drogas endovenosas e parceiro sexual com hepatite, com acurácia discriminante alta para o grupo VHC.

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.

HTLV-1 and neurological conditions: when to suspect and when to order a diagnostic test for HTLV-1 infection? / Doenças neurológicas e infecção pelo HTLV-1: quando suspeitar e quando solicitar testes diagnósticos para a infecção pelo HTLV-1

HTLV-1 is a retrovirus associated with a myriad of clinical conditions, especially hematological and neurological ones. Regarding nervous system diseases, it is of utmost importance to select those cases in which HTLV-1 infection could really be associated. This is particularly true for patients from endemic areas and for HIV-infected patients and drug users, since that these groups are at a higher risk for HTLV infection. This caution in selecting neurological patients for HTLV diagnostic tests is justified by the fact that in some circumstances the seropositivity may merely represent an epiphenomenon. In this paper we enroll some neurological conditions that have been associated with HTLV-1/2 infection in the literature and discuss the real need for HTLV-1/2 diagnostic tests in each one. Because HIV/HTLV-co-infected patients seem to be at an increased risk for neurological diseases development, a special consideration about this matter is also made.

O HTLV-1 é um retrovírus associado tanto a doenças hematológicas quanto a doenças neurológicas. Em relação às doenças neurológicas, é fundamental que selecionemos aquelas em que de fato a infecção pelo HTLV-1 possa ser a causa. Isto é particularmente verdadeiro nos pacientes oriundos de áreas endêmicas e nos pacientes infectados pelo HIV e usuários de drogas, haja vista que estes grupos são de risco para infecção pelo HTLV. Este cuidado ao selecionarmos aquelas condições neurológicas que merecem ser investigadas com sorologia para o HTLV se justifica pelo fato de que nem sempre podemos afastar uma associação fortuita entre a infecção e a referida doença. Neste artigo, comentaremos sobre algumas condições neurológicas que podem estar associadas com a infecção pelo HTLV-1/2, discutindo a real necessidade de solicitar testes para o diagnóstico da infecção pelo HTLV-1/2 frente a elas. Uma breve consideração sobre a co-infecção HIV/HTLV será feita no final deste artigo tendo em vista que estes pacientes apresentam um risco aumentado para o desenvolvimento de doenças neurológicas.

Pautas para el diagnóstico, notificación y asesoramiento de la infección por virus linfotrópico T humano tipo 1 y 2 (HTLV-1/2) en Argentina / Guidelines for the diagnosis, notification and advising for human T-cell lymphotropic virus type 1 and 2 infection in Argentina

El virus linfotrópico T-humano tipo 1 (HTLV-1), primer oncoretrovirus humano descubierto, es el agente etiológico de la Leucemia de Células T del Adulto (ATL) y de la Mielopatía Asociada al HTLV-1 o Paraparesia Espástica Tropical (HAM/TSP). El HTLV-2, no tiene un rol etiológico definido, si bien se lo ha asociado con síndromes neurológicos similares a la HAM/TSP. En Argentina, la detección de anticuerpos para HTLV-1/2 en donantes de sangre es obligatoria desde noviembre de 2005 (resolución 865/2006 del Ministerio de Salud y Ambiente), si bien fue recomendada por la Asociación Argentina de Hemoterapia e Inmunohematología desde el año 1997. Uno de los problemas que se presenta en nuestro país, es la notificación de resultados de esta infección y las dificultades que debe afrontar el médico para brindar la información correcta. En este trabajo se presenta una visión general sobre estos retrovirus, y en especial se brinda información sobre diagnóstico, patogenia y las conductas a seguir por los profesionales de la salud ante la necesi­dad de informar resultados basados únicamente en pruebas de tamizaje o con serología positiva para HTLV­1/2. Para el mismo, nos hemos basado en las recomendaciones y lineamientos elaborados por los Centros de Control de Enfermedades (CDC) y Prevención y el grupo de trabajo del Servicio de Salud Pública de Estados Unidos (USPHS Working Group) dirigidas a las personas infectadas y a trabajadores de la salud e instituciones oficiales de salud pública.

Human T-celllymphotropic virus type 1 (HTLV-1), the first human oncoretrovirus discovered, is the ethiologic agent of Adult T-cell Leukimia (ATL) and HTLV-1 Associated Mielopathy o Tropical Spastic Paraparesis (HAM/TSP). HTLV-2, has not a defined ethiopathology, although it has been associated to neurologic syndroms similar to HAM/TSP Screening for HTLV-1/2 antibodies in blood donors is mandatory since 2005 (Resolution 865/2006 of the Ministry of Health, Argentina) although it has been recomended by the Hemotherapy and Immunehemathology Association since 1997. One of the problems in our country is the notification of the results and the difficulties encountered by the medical doctor in order to provide the appropriate information. In this study, we provide an outlook of these retroviruses, and especially we give information about diagnosis, pathogenesis and guidelines for health professionals when HTLV-1/2 positive serology needs to be notified. We based these recommendations on the guidelines elaborated by the Centers for Disease Control and Prevention and the working group of the US Public Health Service (USPHS Working Group) directed to infected people and to health workers and official institutions of public health.

Performances of HTLV serological tests in diagnosing HTLV infection in high-risk population of São Paulo, Brazil

Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100 percent sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3 percent and 2.5 percent were detected in Group I, and of 9.6 percent and 3.6 percent in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from São Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.

Problemas nos testes diagnósticos de infecção pelos vírus linfotrópicos de células T humanas (HTLV), principalmente HTLV-II, têm sido observados em pacientes com HIV/Aids. Desde Dezembro de 1998, a Seção de Imunologia do Instituto Adolfo Lutz (IAL) oferece a sorologia para HTLV-I/II para Serviços de Saúde Pública que atendem populações consideradas de risco para esta infecção. Duas mil trezentas e doze amostras de soro: 1.393 de Centros de Referência em Aids (Grupo I) e 919 de Clínicas de Especialidade em HTLV (Grupo II) foram encaminhadas para o IAL para a pesquisa de anticorpos anti-HTLV-I/II. A maioria delas foram testadas por dois ensaios imunoenzimáticos (EIAs) e confirmadas por Western Blot (WB 2.4, Genelabs). Sete kits diferentes de EIAs foram empregados durante o período e de acordo com os resultados do WB a melhor performance foi obtida com os EIAs que continham lisado viral dos HTLV-I e -II e a rgp21 como antígenos. Nenhum kit de EIA de 1ª, 2ª ou 3ª geração foi 100 por cento sensível para detectar todas as amostras verdadeiramente HTLV-I/II reagentes. A prevalência de HTLV-I e HTLV-II, respectivamente, foi de 3,3 por cento e 2,5 por cento no Grupo I e de 9,6 por cento e 3,6 por cento no Grupo II. Em ambos os Grupos, foram detectadas altas percentagens de soros com padrão indeterminado no WB. O algoritmo de testes sorológicos para ser usado em população de alto risco para HTLV de São Paulo, Brasil, necessita de dois kits EIAs de princípios e composição diferentes para a triagem sorológica e, pelo elevado número de WB indeterminado, talvez de um outro teste confirmatório.

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

The current diagnosis of human T-lymphotropic virus type-2 (HTLV-2) infection is based on the search of specific antibodies; nevertheless, several studies conducted in Brazil pointed deficiencies of the commercially available kits in detecting HTLV-2, mostly in HIV/AIDS patients. This study searched for the presence of HTLV-1 and -2 in 758 HIV/AIDS patients from Londrina, Paraná, Brazil. Serum samples were screened for HTLV-1/2 antibodies using two EIA kits (Vironostika and Murex), and confirmed by WB (HTLV Blot 2.4, Genelabs). The results obtained by EIA disclosed 49 (6.5 percent) reactive sera: 43 positive by both EIA kits, and six with discordant results. WB confirmed HTLV-1 infection in seven samples (0.9 percent) and HTLV-2 in 21 sera (2.8 percent). Negative and indeterminate results were detected in four (0.5 percent) and 16 (2.1 percent) sera, respectively. Blood from 47 out of 49 HTLV seroreactive patients were collected and analyzed for the presence of env, LTR and tax genomic segments of HTLVs by PCR. PCR confirmed six cases of HTLV-1 and 37 cases of HTLV-2 infection (14 out of 16 that were found to be WB indeterminate). Restriction analysis of the env PCR products of HTLV-2 disclosed 36 isolates of HTLV-2a/c subtype, and one of HTLV-2b subtype. These results emphasize the need of improving serologic tests for detecting truly HTLV-2 infected patients from Brazil, and confirm the presence of HTLV-2b subtype in the South of this country.

O diagnóstico de infecção por HTLV-2 se baseia na pesquisa de anticorpos específicos, entretanto, vários estudos conduzidos no Brasil têm apontado falhas nos kits sorológicos disponíveis no mercado em detectar HTLV-2, principalmente nos pacientes com HIV/aids. Este trabalho avaliou a presença de infecção por HTLV-1 e -2 em 758 pacientes HIV/aids de Londrina, Paraná, Brasil. Amostras de soro foram analisadas quanto à presença de anticorpos anti-HTLV-1/2 por dois kits de EIA (Vironostika e Murex) e confirmados por WB (HTLV Blot 2.4, Genelabs). Os resultados obtidos pelos testes sorológicos mostraram 49 (6,5 por cento) soros reagentes: 43 positivos para ambos os kits e seis com resultados discordantes. O WB confirmou infecção por HTLV-1 em sete soros (0,9 por cento) e HTLV-2 em 21 soros (2,8 por cento). Resultados negativos e indeterminados foram detectados, respectivamente, em quatro (0,5 por cento) e 16 (2,1 por cento) soros. Amostras de sangue de 47 dos 49 pacientes com sorologia reagente foram avaliadas quanto à presença de segmentos do genoma dos HTLVs (env, LTR e tax), usando a técnica de PCR. As PCRs confirmaram seis casos de infecção por HTLV-1 e 37 casos por HTLV-2 (14 dos 16 cuja sorologia resultou WB indeterminada). A subtipagem de HTLV-2 por análise de restrição enzimática de produtos da PCR env mostrou 36 isolados de subtipo HTLV-2a/c e um HTLV-2b. Esses resultados reforçam a necessidade de melhorar o diagnóstico de infecção por HTLV-2 no Brasil e confirmam a presença do subtipo HTLV-2b na região sul do país.

Clinical and epidemiological aspects of HTLV-II infection in São Paulo, Brazil: presence of Tropical Spastic Paraparesis/HTLV-Associated Myelopathy (TSP/HAM) simile diagnosis in HIV-1-co-infected subjects / Aspectos clínicos e epidemiológicos da infecção pelo vírus linfotrópico de células T humanas do tipo 2 (HTLV-II) em São Paulo, Brasil: presença de paraparesia espástica tropical/mielopatia associada ao HTLV em pacientes co-infectados pelo HIV-1

In this study, the epidemiological and clinical features observed in solely HTLV-II-infected individuals were compared to those in patients co-infected with HIV-1. A total of 380 subjects attended at the HTLV Out-Patient Clinic in the Institute of Infectious Diseases "Emilio Ribas" (IIER), São Paulo, Brazil, were evaluated every 3-6 months for the last seven years by infectious disease specialists and neurologists. Using a testing algorithm that employs the enzyme immuno assay, Western Blot and polymerase chain reaction, it was found that 201 (53 percent) were HTLV-I positive and 50 (13 percent) were infected with HTLV-II. Thirty-seven (74 percent) of the HTLV-II reactors were co-infected with HIV-1. Of the 13 (26 percent) solely HTLV-II-infected subjects, urinary tract infection was diagnosed in three (23 percent), one case of skin vasculitis (8 percent) and two cases of lumbar pain and erectile dysfunction (15 percent), but none myelopathy case was observed. Among 37 co-infected with HIV-1, four cases (10 percent) presented with tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM) simile. Two patients showed paraparesis as the initial symptom, two cases first presented with vesical and erectile disturbances, peripheral neuropathies were observed in other five patients (13 percent), and seven (19 percent) patients showed some neurological signal or symptoms, most of them with lumbar pain (five cases). The results obtained suggest that neurological manifestations may be more frequent in HTLV-II/HIV-1-infected subjects than those infected with HTLV-II only.

Neste estudo, as características epidemiológicas e clínicas observadas nos indivíduos infectados pelo HTLV-II foram comparadas com os pacientes co-infectados com HIV-1. Um total de 380 indivíduos atendidos na clínica do Ambulatório HTLV do Instituto de Infectologia "Emilio Ribas" (IIER), São Paulo, Brasil, foram avaliados a cada 3-6 meses nos últimos sete anos por especialistas em doenças infecciosas e neurologistas. Usando um algoritmo que emprega ensaio imunoenzimático, Western Blot e reação em cadeia de polimerase, foram incluídos 201 (53 por cento) pacientes infectados pelo HTLV-I e 50 (13 por cento) infectados pelo HTLV-II. Trinta e sete (74 por cento) eram co-infectados pelo HTLV-II e HIV-1. Dos 13 (26 por cento) indivíduos unicamente infectados pelo HTLV-II, infecção do trato urinário foi diagnosticada em três, um com vasculite e em dois casos dor lombar e disfunção erétil mas nenhum caso de mielopatia foi observado. Entre 37 pacientes co-infectados com HIV-1, quatro (10 por cento) casos apresentaram com paraparesia espástica tropical/mielopatia associada ao HTLV similar. Dois casos mostraram paraparesia como sintoma inicial, dois outros casos se apresentaram primeiramente com distúrbios vesical e erétil e as neuropatias periféricas foram observadas em cinco pacientes (13 por cento). Outros sete (19 por cento) pacientes mostraram algum sinal ou sintoma neurológico, a maioria deles com dor lombar (cinco casos). Os resultados sugerem que as manifestações neurológicas podem ser mais freqüentes em indivíduos co-infectados pelo HTLV-II/HIV-1 do que nos indivíduos infectados somente pelo HTLV-II.

Tuberculous meningoencephalomyelitis and coinfection with HTLV-I + HTLV-II: case report

Os vírus HTLV-I e HTLV-II são endêmicos em algumas regiões do Brasil, onde uma das doenças associadas, a paraparesia espástica tropical/mielopatia associada ao HTLV (PET/MAH), tem sido diagnosticada em significativo número de pacientes infectados. Nesses indivíduos, a prevalência de tuberculose é maior que na população geral, sugerindo que possa haver um maior risco para esta comorbidade. Relatamos o caso de um homem de 44 anos coinfectado HTLV-I + HTLV-II que desenvolveu meningoencefalomielite por Mycobacterium tuberculosis. O paciente apresentou recuperação clínica parcial, correção da disfunção de barreira hemato-liquórica e negativação no PCR, mediante o tratamento com corticoesteróides e tuberculostáticos.

Molecular characterization of human T-cell lymphotropic virus coinfecting human immunodeficiency virus 1 infected patients in the Amazon region of Brazil

The present work evaluated the epidemiology of human immunodeficiency virus 1/human T-cell lymphotropic virus (HIV-1/HTLV) coinfection in patients living in Belém (state of Pará) and Macapá (state of Amapá), two cities located in the Amazon region of Brazil. A total of 169 blood samples were collected. The sera were tested by enzyme-linked immunosorbent assay to determine the presence of antibodies anti-HTLV-1/2. Confirmation of infection and discrimination of HTLV types and subtypes was performed using a nested polymerase chain reaction targeting the pX and 5' LTR regions, followed by restriction fragment length polymorphism and sequencing analysis. The presence of anti-HTLV1/2 was detected in six patients from Belém. The amplification of the pX region followed by RFLP analysis, demonstrated the presence of HTLV-1 and HTLV-2 infections among two and four patients, respectively. Sequencing HTLV-1 5' LTR indicated that the virus is a member of the Cosmopolitan Group, Transcontinental subgroup. HTLV-2 strains isolated revealed a molecular profile of subtype HTLV-2c. These results are a reflex of the epidemiological features of HIV-1/HTLV-1/2 coinfection in the North region of Brazil, which is distinct from other Brazilian regions, as reported by previous studies.

Estudo das infecções pelo HTLV-I e pelo HTLV-II como fatores prognósticos em uma coorte de portadores do HIV acompanhados em Santos-SP / Study of infection by HTLV-I and HTLV-II as prognostic factors in a cohort of patients with HIV in Santos-SP

Os retrovírus humanos incluem o vírus da imunodeficiência humana (HIV), agente causal da síndrome da imunodeficiência adquirida (AIDS), e os vírus linfotrópicos de células T humanas do tipo I (HTlV-I) e do tipo II (HTlV-II), estes associados etiologicamente a doenças de natureza linfoproliferativa e/ou neurodegenerativa. Apresentam as mesmas formas de transmissão, resultando em fatores comuns de risco e em sobreposição de populações expostas. Embora os três vírus sejam linfotrópicos, o HIV se apresenta com altas taxas de replicação e proporciona a morte celular em todos os estágios da infecção, enquanto o HTLV-I e o HTLV-II podem causar proliferação e eventualmente transformação celular. O efeito do HTLV-I e do HTLV-II sobre o sistema imunológico como um dos fatores que interferem na evolução da AIDS envolve um grande interesse e ainda é motivo de controvérsia. Pesquisas in vitro sugerem que o HTLV-I e o HTLV-II podem aumentar a replicação e a expressão do HIV. Alguns estudos clínico-epidemiológicos apontam na direção de que exista efeito da concomitância das infecções pelo HIV e pelo HTLV-I ou pelo HTLV-II sobre a evolução da progressão da AIDS. Em um estudo anterior, desenvolvido entre portadores do HIV atendidos no Centro de Referência em AIDS de Santos-SP, observou-se uma soroprevalência de 6,0% da infecção pelo HTLV-I e de 7,4% pelo HTLV-II, o que poderia justificar a investigação de possível modificação na evolução da história natural da infecção pelo HIV nesses pacientes co-infectados. O presente trabalho foi desenvolvido, como um estudo de coorte retrospectiva, visando a avaliar o tempo de sobrevida dos portadores do HIV na população estudada e sua associação com as infecções pelo HTLV-I e pelo HTLV-II, bem como com outros fatores prognósticos e marcadores de progressão. Dos 495 portadores do HIV acompanhados entre 1997 e 2002, em um número total de 23.031,5 pacientes-mês, foi observado que 145 pacientes evoluíram para o óbito em decorrência...

Estudo das infecções pelo HTLV-I e pelo HTLV-II como fatores prognósticos em uma coorte de portadores de HIV acompanhados em Santos-SP / Study of infectious caused by HTLV-I and HTLV-II as prognostic factors in a cohort of HIV-positive patients followed up in Santos-SP

HIV-1 e HTLV-I/II apresentam mesmas formas de transmissão. Portadores do HIV em Santos-SP mostraram soroprevalência de 6,0 por cento pelo HTLV-I e de 7,4 por cento pelo HTLV-II. O estudo avaliou fatores associados com o tempo de sobrevida dos portadores do HIV. De 495 pacientes, 145 morreram por AIDS entre 1997 e 2002. Análise de Cox indicou associação do óbito com: raça negra (HRajust 1,50-IC95 por cento 1,03-2,17) menos de 3 anos de escolaridade (HRajust 1,90-IC95 por cento 1,12-3,25) menos de 200 CD4+/mm³ (HR ajust 4,44-IC95 por cento 2,70-7,31) classe B ou C CDC (HR ajust 3,63-IC95 por cento 1,54-8,56) anti-HTLV-I (HRajust 1,95-IC95 por cento 1,08-3,52) anti-HCV (HRajust 1,76-IC95 por cento 1,20-2,60) e menor exposição a HAART (HRajust 2,36-IC95 por cento 1,61-3,45)/HIV-1 and HTLV-I/II have similar transmission patterns. A seroprevalence of 6 per cent for HTLV-I and of 7.4 per cent for HTLV-II was observed in HIV patients in Santos-SP. The study evaluated factors associated to the survival of HIV patients. From 495 individuals, 145 died of AIDS between 1997 and 2002. Cox analysis indicated association between death and variables: black race (adj HR 1.50 95 per cent CI 1.03-2.17), less than three-year education (adj HR 1.90 95 per cent CI 1.12-3.25), less than 200 CD4+/mm3 (adj HR 4.44 95 per cent CI 2.70-7.31), CDC class B or C (adj HR 3.63 95 per cent CI 1.54-8.56), anti-HTLV-I (adj. HR 1.95 95 per cent CI 1.08-3.52), anti-HCV (adj HR 1.76 95 per cent CI 1.20-2.60) and shorter use of HAART (adj HR 2.36 95 per cent CI 1.61-3.45)...

Erectile insufficiency as first symptom of HTLV I/II associated myelopathy: case report

A case of HTLV-I/II myelopathy in which the initial complaint was erectile insufficiency (EI) is reported. The only abnormalities found on the neurological exam were discrete weakness of the psoas and increased knee jerk reflexes. Diagnosis was male by demonstrating antibodies anti-HTLV I/II in the serum and cerebrospinal fluid (with the techniques of ELISA and Western blot), with confirmation by the polymerase chaim reaction (PCR). El can thus be the first symptom of HTLV-I/II infection and patients with EI of unknown etiology should be tested for HTLV-I/II in endemic areas.

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula

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.