RESUMO
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%) and 6 women (23.1%) had detectable antibodies against HTLV-I/II. The major risk factor associated with coinfection by HTLV was intravenous drug use (57.7% of coinfected patient versus 9.2% 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 ± 177 cells/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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções por HTLV-II/complicações , Estrongiloidíase/etiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Relação CD4-CD8 , Feminino , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/imunologia , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/imunologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologiaRESUMO
BACKGROUND: Although cyclophosphamide based regimens can produce remission rates approaching 60 to 80% in endemic Burkitts lymphoma, relapses and refractory disease are fairly common in developing countries, due to advanced stage disease and cost-constraints in the implementation of optimal chemotherapeutic protocols. OBJECTIVE: To evaluate an affordable, tolerable and targeted approach to chemotherapy for endemic Burkitt's lymphoma as would be desirable in resource poor settings such as Africa. METHOD: We present data and review pertinent literature that indicates that the antiviral agent Zidovudine specifically targets this tumour through a unique and novel mechanism. DATA SOURCE: Our original studies, publications original and review articles searched in Pubmed indexed for Medline. DATA EXTRACTION: A systematic review to identify studies relating to Zidovudine, EBV+ and Burkitt's lymphoma, indicating antiviral agents zidovudine targeting BL in a unique and novel mechanisms. DATA SYNTHESIS: Our data and a qualitative assessment of the relevant literature was undertaken, given the heterogenicity of the study types making it inappropriate to pool results across studies. CONCLUSION: Our data suggests that the incorporation of Zidovudine into Burkitt's regimens may enhance tumour kill and abbreviate the duration of treatment necessary for this disease. Furthermore, the addition of the widely available and inexpensive agent hydroxyurea, markedly potentiates the tumorcidal activity of Zidovudine in Epstein Barr virus positive Burkitt's lymphomas. We recommend that further clinical studies in patients afflicted with this disease are needed to clearly define this potential use of Zidovudine.
Assuntos
Antivirais/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Zidovudina/uso terapêutico , África , Antivirais/farmacologia , Brasil , Linfoma de Burkitt/virologia , Países em Desenvolvimento , Sistemas de Liberação de Medicamentos , Marcação de Genes , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/genética , Humanos , Oncogenes , Zidovudina/farmacologiaRESUMO
To better understand the origin of human T-cell leukemia virus type l (HTLV-l) in South America, we conducted a phylogenetic study on 27 new HTLV-ls in Brazil. These were obtained from Brazilians of various ethnic origins, such as Japanese immigrants, whites, blacks and mulattos. We amplified and sequenced proviral DNAs of a part of the long terminal repeats. Phylogenetic trees revealed that all but 6 of the new isolates were not only similar to each other but also similar to HTLV-ls of other South American countries, including those from Amerindians. However, the isolates differed from the HTLV-ls of Africa and Japan. The other six isolates were from Japanese immigrants and were phylogenetically almost identical to HTLV-ls in Japan but different from the majority of South American HTLV-ls, including the other new Brazilian HTLV-ls. These findings indicate that the recent introduction of HTLV-1 from Japan is limited to Japanese immigrants. In addition, the results do not support the prevailing hypothesis that HTLV-ls in South America were introduced by blacks who were brought from Africa as slaves. Rather, these results suggest that the majority of HTLV-1s prevailing in South America have spread from Amerindians, some of whom are likely to have possessed this human retrovirus from the beginning of their settlement in South America.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Filogenia , Adulto , África , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Brasil/epidemiologia , Emigração e Imigração , Etnicidade , Feminino , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Sequências Repetidas Terminais/genéticaRESUMO
The state of Bahia in the northeastern coast of Brazil is a region in which HTLV-I infection is endemic. This study investigated the characteristics of 28 HTLV-I-associated lymphomas/leukemias in this region. HTLV-I-infection diagnosis was based on serologic study, Southern blot analysis, and polymerase chain reaction (PCR) in neoplastic tissue. The main clinical differences between these lymphomas and adult T-cell leukemia (ATL) cases from other endemic areas were as follows. The mean age was 47 years; 20% of the cases occurred in young adults; and a predominance was found among male subjects (2:1), blacks, and of those of mixed race (96%). Histologically, 20 cases were T-cell pleomorphic leukemia/lymphoma, 5 were Mycosis fungoides-like cutaneous lymphoma, and 3 were CD30+ large-cell anaplastic lymphoma. Immunohistochemistry demonstrated 4 cases of CD8+ lymphoma. Proviral genomic sequences were demonstrated by PCR in 9 lymph node biopsy specimens and in 3 skin biopsy specimens. Southern blot was performed and was positive in 8 cases.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , Western Blotting , Brasil/epidemiologia , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HTLV-I/sangue , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Soroepidemiológicos , Distribuição por Sexo , Pele/patologiaRESUMO
To evaluate the viral load in peripheral blood mononucler cells (PBMC) of patients infected by HIV-1 we performed 96 quantitative cultures in 74 patients infected by HIV-1, using the co-culture method. The viral load was expressed in tissue culture infectious doses (TCID), and the results were analyzed according to gender, age and clinical stage of patients, duration of previous antiretroviral therapy, detectable p24 antigenemia, CD4(+)/CD8(+) cell counts, co-infection by HTLV-I/II and viral subtype. We detected a statistically significant association between co-infection by HTLV-I/II and viral load higher than >50 TCID (p=0.003). We also found a significant association between co-infection by HTLV-I/II and p24 antigenemia (p=0.028). CD4(+) cell counts were significantly higher for patients presenting negative cultures, but there was no detectable association between lower CD4(+) cell counts and higher TCID. The majority of patients were infected by subtype B virus. The observation in this study that co-infection with HTLV-I/II was significantly associated with higher viral load raises the possibility that these agents act as co-factors of AIDS progression, in doubly-infected patients.
RESUMO
During 2 1/2 year period,378 patients diagnosed with tuberculosis and admitted to a general hospital for care of the poor in Salvador, Bahia, were tested serologically for HIV-1, HTLV-I, and HTLV-II. The patients' mean age was 41.8 (range 14-89); they were hospitalized for a mean of 62 +/- 43 days; 70% were being treated for the first time; most of the remainder were being retreated after non-compliance with previously recommended anti-tuberculosis medication and a few required second-line therapy for relapsed disease. None had had previous serologic testing for retroviruses. Among the study population, 59 (16%) were found to be positive for retroviral infection. The distribution was as follows: 18 (4.8%) had HIV-1, 32 (8.5%) had HTLV-I, 2 of these had both HTLV-l and HTLV-II, 9 (2.4%) had both HIV-1 and HTLV-I. The rates of positive serologic tests for retroviral infection in this Salvador is 0.2% for HIV-1 and 1.0% for HTLV-I. Thus, there is a higher than expected frequency of retroviral infections among patients hospitalized for treatment of tuberculosis. The prognosis for treated patients was determined by recording the cause of death and the mortality rate. In the 319 patients with negative serologic testing for retroviruses there were 25 deaths (8%). In 32 patients with HTLV-I infection there were 8 deaths (25%), and in 18 patients with HIV-1 infection there were 6 deaths (33%). In 9 patients with both HIV-1 and HTLV-I there were 5 deaths (56%). The causes of death in each serological group were primarily related to progression of tuberculosis rather than complications of rapid progression of the retroviral infection. We conclude that co-infection and disease due to either HIV-1 or HTLV-I/II infection and tuberculosis is common, that the occurrence of HTLV-I in this population is higher than previously recognized, and that prognosis associated with the management of tuberculosis is adversely affected by the presence of either retroviral infection. In a few patients with both retroviral infections, mortality was very high. All patients with tuberculosis should be tested for retroviral infection because of the prognostic and therapeutic implications.
RESUMO
Serum samples from 895 HIV-1 infected individuals were tested for antibodies against HTLV-I and HTLV-II. The overall prevalence of the co-infection was high (16.3%). Epidemiological information was obtained from each subject including gender, age, intravenous drug use (IVDU), blood transfusion, previous diagnosis of sexually transmitted diseases (STD) and sexual behavior. The risks for acquiring retroviral infections other than HIV-1 were evaluated and the prevalence of co-infection was compared according to the AIDS clinical status. We detected seven cases (0.9%) of triple infection. HTLV-I co-infection was associated with blood transfusion (p=0.02), IVDU (p=0.0001) and female gender (p=0.0001). Co-infection by HTLV-II was primarily associated with a history of past blood transfusion (p=0.009). Women co-infected by HTLV-I or HTLV-II had a higher risk of AIDS than those infected only by HIV-1 (RR=2.04; 95% CI: 127-327, p=0.007 and RR=3.09; 95% CI: 1.07-8.91, p=0.04, respectively). These findings suggest that co-infection by HTLVI or II in Bahia, Brazil, may modify the clinical course of HIV-1 infection.
Assuntos
DNA Viral/isolamento & purificação , Infecções por Herpesviridae/diagnóstico , Argentina/epidemiologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/epidemiologia , Humanos , Masculino , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/virologia , Homologia de Sequência do Ácido NucleicoRESUMO
Human T cell lymphotropic virus type II (HTLV-II) infection is endemic in a number of indigenous populations in North, Central, and South America. In the present study we have employed serological and molecular methods to identify HTLV-II infection in Indian communities in the Amazon region of Brazil. Sera (1324) from 25 different Indian communities were analyzed by ELISA and Western blot. One hundred and four samples (7.8%) from a number of culturally distinct and geographically unrelated populations were found to have reactivities consistent with HTLV-II infection. Of these, 67 were from the Kayapo Indian communities, which had an overall seroprevalence rate of greater than 30%. In addition, high seroprevalence rates were observed in three other communities, the Munduruku, Arara do Laranjal and the Tyrio, suggesting that there are additional foci of endemic infection in the Amazon region. In the Kayapo, seroprevalence rates tended to increase with age, supporting the importance of sexual transmission of the virus, and family studies demonstrated that vertical transmission is also an important route of infection. Restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis of a region of the env gene demonstrated that the Kayapo are infected with the HTLV-IIa subtype. Moreover, nucleotide sequence analysis of the LTR demonstrated that this belonged to a distinct HTLV-IIa phylogenetic group. The identification of HTLV-IIa in the Kayapo is, as far as we are aware, the first identified endemic focus of infection by this subtype of HTLV-II in the Americas.
Assuntos
Genes env , Anticorpos Anti-HTLV-II/sangue , Infecções por HTLV-II/epidemiologia , Vírus Linfotrópico T Tipo 2 Humano/genética , Indígenas Sul-Americanos/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Sequência de Bases , Western Blotting , Brasil/epidemiologia , Criança , Pré-Escolar , Primers do DNA , Feminino , Geografia , Infecções por HTLV-II/transmissão , Vírus Linfotrópico T Tipo 2 Humano/classificação , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Caracteres Sexuais , Fatores SexuaisRESUMO
There are 2 subtypes of human T-cell lymphoma/leukemia virus type II (HTLV-II), A and B. HTLV-II is increasingly associated with rare forms of lymphocytic neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene from many isolates of HTLV-IIA and HTLV-IIB from around the world. Analysis of these and other published sequence established that all HTLV-IIA sequences contained a unique Hinf I site and all HTLV-IIB sequences a unique Mse I site. A rapid and specific oligomer restriction (OR) assay was developed utilizing the primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance between sequenced and OR-based subtyping of DNA amplified by PCR was absolute among 22 HTLV-II isolates tested. Further OR or sequence analyses on an additional 30 other isolates indicated that the majority of North American non-indian HTLV-II isolates were subtype A, while all Paleo-Amerindian samples, including those from the Seminole of Florida; the Guaymi from Panama; and the Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The SK110/SK111 PCR-OR format should facilitate molecular epidemiology studies of HTLV-II infection and allow for subtype stratification in assessing the sensitivity and specificity of HTLV detection formats and HTLV-II disease association.
Assuntos
DNA Viral/sangue , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Argentina , Sequência de Bases , Primers do DNA , Feminino , Genes pol/genética , Vírus Linfotrópico T Tipo 2 Humano/classificação , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Sensibilidade e Especificidade , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Estados Unidos , Proteínas Virais/análiseRESUMO
We compared the performance of a rapid and simple anti-CD4 antibody-coated microsphere assay with flow cytometry and immunofluorescence for quantitation of absolute count of CD4+ T lymphocytes. A longitudinal evaluation of CD4+ T lymphocytes by flow cytometry and microsphere assay in 10 human immunodeficiency virus (HIV)-seronegative and 59 HIV-seropositive individuals was conducted over a period of 9 months. Standard flow cytometry analysis was performed to establish the absolute CD4+ T-lymphocyte count. The microsphere assay uses whole blood; CD14+ and CD4+ cells are first blocked by small latex beads coated with anti-CD14 antibody, and remaining cells are stained with larger anti-CD4 antibody-coated beads. Cells rosetted with only anti-CD4 antibody-coated beads are counted with use of a hemacytometer. Immunofluorescence microscopy was performed by standard techniques with use of peripheral blood mononuclear cells. The predictive value for stratification of HIV-seropositive patients by CD4+ T-lymphocyte values of < 200/microliters was 95% when the microsphere method was compared with flow cytometry. A correlation coefficient of 0.91 between the two assay methods was demonstrated in 281 CD4+ T-lymphocyte tests for absolute count. Finally, the flow cytometry method yielded better results than did the microsphere assay and immunofluorescence microscopy, in descending order of accuracy. The microsphere method should be effective in determining absolute CD4+ T-lymphocyte count in developing countries where, for a variety of reasons, no other method can be reliably performed.
Assuntos
Contagem de Linfócito CD4/métodos , Soropositividade para HIV/imunologia , Estudos de Coortes , Estudos de Avaliação como Assunto , Citometria de Fluxo , Imunofluorescência , Soronegatividade para HIV/imunologia , Soropositividade para HIV/sangue , Humanos , Microesferas , Estudos Prospectivos , Formação de Roseta , Sensibilidade e EspecificidadeRESUMO
A case of a 20-years-old black man from Salvador, Bahia with HTLV-I associated T cell lymphoma is presented. In spite of the absence of splenomegaly and leukemia, the patient had a marked cephalic tumoral infiltration associated with axillary tumors in a pattern not yet described in adult T cell lymphoma. Peripheral blood involvement was observed later on in the course of the disease. The patient underwent chemotherapy but died seven months after diagnosis.
Assuntos
Leucemia-Linfoma de Células T do Adulto/patologia , Infiltração Leucêmica/patologia , Pele/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Face/patologia , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/imunologia , Infiltração Leucêmica/tratamento farmacológico , Masculino , Prednisona/administração & dosagem , Prognóstico , Vincristina/administração & dosagemAssuntos
Portador Sadio/epidemiologia , Infecções por HTLV-II/diagnóstico , Infecções por HTLV-II/epidemiologia , Indígenas Sul-Americanos , Western Blotting , Portador Sadio/sangue , Colômbia/epidemiologia , DNA Viral/sangue , Feminino , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/diagnóstico , Anticorpos Anti-HTLV-II/sangue , Infecções por HTLV-II/sangue , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , MasculinoRESUMO
We investigated the prevalence of human T-lymphotropic virus I/II (HTLV-I/II) infection in Bahia, a state in Northeastern Brazil. Healthy individuals (n = 327) and patients (n = 337) with a variety of diseases were screened for antibodies to HTLV-I/II using an enzyme immunoassay and Western blot. The overall prevalence among healthy subjects was 1.8% (six of 327); among patients it was 18.4% (62 of 337). Patients with AIDS had the highest prevalence of HTLV-I/II infection, 22.7% (20/88), followed by randomly selected patients from an infectious disease hospital, 19.4% (25 of 129), and tuberculosis patients, 11.1% (10 of 90). Four of 14 patients with myelopathy and three of 16 patients with lymphoid leukemia or lymphoma were seropositive for HTLV-I/II. Sixty-three of 68 HTLV-I/II-positive specimens were then typed: 53 patients were HTLV-I positive, three patients were HTLV-II positive, and in seven patients the assay could not distinguish infection by HTLV-I or II. The finding among HIV-seropositive intravenous drug users in Bahia of coinfection with HTLV-I is contrasted with reports from other areas in which dual infection occurs with HTLV-II. Although high prevalence of HTLV-I infection was found in Bahia, the extent and clinical manifestations of HTLV-I/II infection in Brazil remains imprecisely defined, and further studies are needed.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-II/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/complicações , Anticorpos Anti-HTLV-II/sangue , Infecções por HTLV-II/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Fatores de Risco , Fatores Sexuais , Abuso de Substâncias por Via Intravenosa/complicações , Tuberculose/complicaçõesRESUMO
Jamaican Neuropathy of the ataxic type (tropical ataxic neuropathy [TAN] and spastic type (tropical spastic paraparesis [TSP]) have been recognized for over a century in Jamaica. The recent association of TSP with HTLV-I (TSP/HAM) is now well established. We now present evidence for a possible association between a TAN-like illness with HTLV-II in four females aged 34-49. All presented with ataxic gait and all four have prominent mental changes. Three of the four also have minor motor deficits with urinary frequency and two have nocturnal leg cramps. All have serum antibody and all had PCR evidence of HTLV-II infection. Antibody to HTLV-II is present in CSF from two subjects. The distinctive picture of prominent ataxia and altered mental status in these subjects contrasts with a predominantly myelopathic picture seen in TSP/HAM.