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1.
World J Gastroenterol ; 23(30): 5549-5556, 2017 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-28852314

RESUMEN

AIM: To identify environmental risk factors associated with the development of Crohn's disease (CD) in order to re-assess the hygiene hypothesis. METHODS: A hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTS: On the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSION: Most variables supporting the "hygiene hypothesis" are associated with the development of CD but are not independent predictors of the diagnosis.


Asunto(s)
Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Hipótesis de la Higiene , Fumar/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Apendicectomía/efectos adversos , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Factores Sexuales , Clase Social , Encuestas y Cuestionarios , Adulto Joven
2.
Braz. j. infect. dis ; 21(3): 317-324, May-June 2017. tab, graf
Artículo en Inglés | LILACS-Express | ID: biblio-839213

RESUMEN

ABSTRACT Introduction: The Mycobacterium tuberculosis East African-Indian (EAI) spoligotyping family (belonging to lineage 1, Indo-Oceanic, defined by the region of deletion RD239) is distributed worldwide, but is more prevalent in Southeast Asia, India, and East Africa. Studies in Latin America have rarely identified EAI. In this study, we describe the occurrence of the EAI family in Brazil. Methods: EAI was identified in a systematic literature review of genetic diversity studies pertaining to M. tuberculosis in Brazil, as well as in a survey conducted in Salvador, Bahia, located in the northeastern region of this country. Results: The EAI6-BGD1 spoligotyping family and the EAI5 Spoligotype International Type (SIT) 1983 clade were the most frequently reported, with wide distribution of this particular clade described in Brazil. The distribution of other EAI spoligotyping patterns with broader worldwide distribution was restricted to the southeastern region of the country. Conclusions: EAI may be endemic at a low frequency in Brazil, with some clades indicating increased fitness with respect to this population.

3.
Braz J Infect Dis ; 21(3): 317-324, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28238627

RESUMEN

INTRODUCTION: The Mycobacterium tuberculosis East African-Indian (EAI) spoligotyping family (belonging to lineage 1, Indo-Oceanic, defined by the region of deletion RD239) is distributed worldwide, but is more prevalent in Southeast Asia, India, and East Africa. Studies in Latin America have rarely identified EAI. In this study, we describe the occurrence of the EAI family in Brazil. METHODS: EAI was identified in a systematic literature review of genetic diversity studies pertaining to M. tuberculosis in Brazil, as well as in a survey conducted in Salvador, Bahia, located in the northeastern region of this country. RESULTS: The EAI6-BGD1 spoligotyping family and the EAI5 Spoligotype International Type (SIT) 1983 clade were the most frequently reported, with wide distribution of this particular clade described in Brazil. The distribution of other EAI spoligotyping patterns with broader worldwide distribution was restricted to the southeastern region of the country. CONCLUSIONS: EAI may be endemic at a low frequency in Brazil, with some clades indicating increased fitness with respect to this population.


Asunto(s)
Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Mycobacterium tuberculosis/genética , Brasil , Genotipo , Mycobacterium tuberculosis/clasificación , Filogeografía
4.
PLoS One ; 9(10): e107747, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25314118

RESUMEN

Rio de Janeiro is endemic for tuberculosis (TB) and presents the second largest prevalence of the disease in Brazil. Here, we present the bacterial population structure of 218 isolates of Mycobacterium tuberculosis, derived from 186 patients that were diagnosed between January 2008 and December 2009. Genotypes were generated by means of spoligotyping, 24 MIRU-VNTR typing and presence of fbpC103, RDRio and RD174. The results confirmed earlier data that predominant genotypes in Rio de Janeiro are those of the Euro American Lineages (99%). However, we observed differences between the classification by spoligotyping when comparing to that of 24 MIRU-VNTR typing, being respectively 43.6% vs. 62.4% of LAM, 34.9% vs. 9.6% of T and 18.3% vs. 21.5% of Haarlem. Among isolates classified as LAM by MIRU typing, 28.0% did not present the characteristic spoligotype profile with absence of spacers 21 to 24 and 32 to 36 and we designated these conveniently as "LAM-like", 79.3% of these presenting the LAM-specific SNP fbpC103. The frequency of RDRio and RD174 in the LAM strains, as defined both by spoligotyping and 24 MIRU-VNTR loci, were respectively 11% and 15.4%, demonstrating that RD174 is not always a marker for LAM/RDRio strains. We conclude that, although spoligotyping alone is a tool for classification of strains of the Euro-American lineage, when combined with MIRU-VNTRs, SNPs and RD typing, it leads to a much better understanding of the bacterial population structure and phylogenetic relationships among strains of M. tuberculosis in regions with high incidence of TB.


Asunto(s)
Repeticiones de Minisatélite/genética , Mycobacterium tuberculosis/genética , Polimorfismo de Nucleótido Simple , Tuberculosis/microbiología , Alelos , Proteínas Bacterianas/genética , Brasil , Frecuencia de los Genes , Genotipo , Humanos , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia
5.
Artículo en Inglés | MEDLINE | ID: mdl-24904240

RESUMEN

BACKGROUND: There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. METHODS: This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. RESULTS: There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. CONCLUSIONS: We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests.


Asunto(s)
Artritis Juvenil , Ensayo de Immunospot Ligado a Enzimas/métodos , Tuberculosis Latente , Metotrexato , Mycobacterium tuberculosis/aislamiento & purificación , Prueba de Tuberculina/métodos , Adolescente , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/epidemiología , Artritis Juvenil/inmunología , Brasil/epidemiología , Niño , Femenino , Humanos , Huésped Inmunocomprometido/inmunología , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/etiología , Estudios Longitudinales , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Prevalencia , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
Infect Genet Evol ; 18: 238-46, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23648425

RESUMEN

Human tuberculosis is an infectious disease caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Although spoligotyping and MIRU-VNTR are standard methodologies in MTBC genetic epidemiology, recent studies suggest that Single Nucleotide Polymorphisms (SNP) are advantageous in phylogenetics and strain group/lineages identification. In this work we use a set of 79 SNPs to characterize 1987 MTBC isolates from Portugal and 141 from Northeast Brazil. All Brazilian samples were further characterized using spolygotyping. Phylogenetic analysis against a reference set revealed that about 95% of the isolates in both populations are singly attributed to bacterial lineage 4. Within this lineage, the most frequent strain groups in both Portugal and Brazil are LAM, followed by Haarlem and X. Contrary to these groups, strain group T showed a very different prevalence between Portugal (10%) and Brazil (1.5%). Spoligotype identification shows about 10% of mis-matches compared to the use of SNPs and a little more than 1% of strains unidentifiability. The mis-matches are observed in the most represented groups of our sample set (i.e., LAM and Haarlem) in almost the same proportion. Besides being more accurate in identifying strain groups/lineages, SNP-typing can also provide phylogenetic relationships between strain groups/lineages and, thus, indicate cases showing phylogenetic incongruence. Overall, the use of SNP-typing revealed striking similarities between MTBC populations from Portugal and Brazil.


Asunto(s)
Mycobacterium tuberculosis/genética , Tuberculosis/epidemiología , Tuberculosis/microbiología , Brasil/epidemiología , Análisis por Conglomerados , ADN Bacteriano/genética , ADN Intergénico/genética , Humanos , Epidemiología Molecular , Tipificación Molecular , Mycobacterium tuberculosis/clasificación , Filogenia , Polimorfismo de Nucleótido Simple , Portugal/epidemiología
7.
Tuberculosis (Edinb) ; 92(3): 218-25, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22391089

RESUMEN

BACKGROUND: The existence of ectosome-like microvesicles released by neutrophils was proposed a few decades ago. Other studies revealed that the innate immune response during mycobacterial infection is accompanied by an intense migration of neutrophils to the site of infection, which may be important during the acute phase of tuberculosis. We found that the ectosomes derived from infected neutrophils are biologically active and can influence the survival of Mycobacterium tuberculosis within macrophages. METHODS: Mycobacteria were cultured on supplemented Middlebrook-7H9 broth. All strains were grown to the exponential phase and quantitated by serial dilution. Human neutrophils and macrophages were infected with mycobacteria. Ectosomes from neutrophils were isolated post-infection and characterized by transmission electron microscopy and flow cytometry. To determine whether these microvesicles influenced mycobactericidal activity, mycobacteria-infected macrophages were treated with isolated ectosomes. RESULTS: Ectosomes were released from neutrophils infected with mycobacteria. These ectosomes were derived from neutrophil plasma membrane and a small proportion stained with PKH26. These microvesicles, when incubated with infected macrophages, influenced antimycobacterial activity. CONCLUSIONS: This is the first study to demonstrate that ectosomes that are shed from infected neutrophils influence mycobactericidal activity in macrophages in vitro, suggesting that these microvesicles have biological significance. Nevertheless, major gaps in our knowledge of microvesicle biology remain.


Asunto(s)
Micropartículas Derivadas de Células/inmunología , Activación de Macrófagos/inmunología , Mycobacterium tuberculosis/inmunología , Neutrófilos/inmunología , Tuberculosis/inmunología , Comunicación Celular/inmunología , Micropartículas Derivadas de Células/ultraestructura , Células Cultivadas , Colorantes Fluorescentes , Humanos , Macrófagos/inmunología , Macrófagos/microbiología , Microscopía Electrónica , Neutrófilos/microbiología , Neutrófilos/ultraestructura , Compuestos Orgánicos
8.
J Bras Pneumol ; 37(5): 664-8, 2011.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-22042400

RESUMEN

In 2005 and 2006, 8,121 clinical specimens submitted to the Mycobacteriology Laboratory of the Clementino Fraga Filho University Hospital/Thoracic Diseases Institute, in the city of Rio de Janeiro, Brazil, were inoculated on Löwenstein-Jensen medium containing glycerol and pyruvate. There were 79 mycobacteria isolates that presented growth only on pyruvate-containing medium, and those isolates were selected for the presumptive identification of Mycobacterium bovis. The selected isolates were screened with biochemical tests, PCR amplification (with the specific primers Rv0577 and Rv1510), and pyrazinamide susceptibility tests. All of the strains isolated showed specific phenotypical and genotypical patterns characteristic of M. tuberculosis, and no M. bovis strains were detected.


Asunto(s)
Mycobacterium bovis/crecimiento & desarrollo , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/microbiología , Técnicas Bacteriológicas/métodos , Brasil/epidemiología , Medios de Cultivo/química , Hospitales Universitarios , Humanos , Mycobacterium tuberculosis/clasificación , Tuberculosis/epidemiología
9.
J. bras. pneumol ; 37(5): 664-668, set.-out. 2011. tab
Artículo en Portugués | LILACS | ID: lil-604395

RESUMEN

Entre 2005 e 2006, 8.121 espécimes clínicos enviados ao Laboratório de Micobactérias do Hospital Universitário Clementino Fraga Filho/Instituto de Doenças do Tórax, no Rio de Janeiro, RJ, foram inoculados em meio Löwenstein-Jensen contendo glicerol e piruvato. Desses espécimes, 79 isolados de micobactérias tiveram crescimento somente em meio com piruvato, sendo selecionados para a identificação presuntiva de Mycobacterium bovis. Esses isolados foram submetidos à identificação por testes bioquímicos, amplificação por PCR com primers específicos (Rv0577 e Rv1510) e teste de suscetibilidade à pirazinamida. Todas as cepas apresentaram padrões fenotípicos e genotípicos de M. tuberculosis, não sendo detectado M. bovis.


In 2005 and 2006, 8,121 clinical specimens submitted to the Mycobacteriology Laboratory of the Clementino Fraga Filho University Hospital/Thoracic Diseases Institute, in the city of Rio de Janeiro, Brazil, were inoculated on Löwenstein-Jensen medium containing glycerol and pyruvate. There were 79 mycobacteria isolates that presented growth only on pyruvate-containing medium, and those isolates were selected for the presumptive identification of Mycobacterium bovis. The selected isolates were screened with biochemical tests, PCR amplification (with the specific primers Rv0577 and Rv1510), and pyrazinamide susceptibility tests. All of the strains isolated showed specific phenotypical and genotypical patterns characteristic of M. tuberculosis, and no M. bovis strains were detected.


Asunto(s)
Humanos , Mycobacterium bovis/crecimiento & desarrollo , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/microbiología , Técnicas Bacteriológicas/métodos , Brasil/epidemiología , Medios de Cultivo/química , Hospitales Universitarios , Mycobacterium tuberculosis/clasificación , Tuberculosis/epidemiología
10.
J Med Microbiol ; 60(Pt 10): 1441-6, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21596907

RESUMEN

We performed genotyping of Mycobacterium leprae present in skin biopsy samples that were collected during the first and the second disease occurrences from eight leprosy patients, seven of whom were diagnosed as suffering from disease relapse. Sequence analysis of part of the M. leprae rpoB, folP1, gyrB and gyrA genes did not show genetic change that supported the presence of drug-resistant bacilli. However, we observed a synonymous nucleotide change at position 297 of gyrA among five of these patients, one presenting C to T (CgyrAT) and four presenting T to C (TgyrAC) at this position. Additional genotyping by analysis of the four short tandem repeats GAA, GTA9, AT17 and TA18 showed that the gyrA single nucleotide polymorphism change was accompanied by a change in short tandem repeat genotype. Our data suggest that leprosy relapse in these patients, living in an area endemic for leprosy, could be caused by M. leprae with a genotype different from the one that caused initial disease.


Asunto(s)
Lepra/epidemiología , Lepra/microbiología , Tipificación Molecular , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Adulto , Anciano , Proteínas Bacterianas/genética , Biopsia , Brasil/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Recurrencia , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN , Piel/microbiología
11.
Tuberculosis (Edinb) ; 91(1): 14-21, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21106441

RESUMEN

The contribution of Mycobacterium bovis to the global burden of tuberculosis (TB) in man is likely to be underestimated due to its dysgonic growth characteristics and because of the absence of pyruvate in most used media is disadvantageous for its primary isolation. In Brazil Mycobacterium culture, identification and susceptibility tests are performed only in TB reference centers, usually for selected cases. Moreover, solid, egg-based, glycerol-containing (without pyruvate supplementation) Löwenstein-Jensen (L-J) or Ogawa media are routinely used, unfavouring M. bovis isolation. To determine the importance of M. bovis as a public health threat in Brazil we investigated 3046 suspected TB patients inoculating their clinical samples onto routine L-J and L-J pyruvate enriched media. A total of 1796 specimens were culture positive for Mycobacterium spp. and 702 TB cases were confirmed. Surprisingly we did not detect one single case of M. bovis in the resulting collection of 1674 isolates recovered from M. bovis favourable medium analyzed by conventional and molecular speciation methods. Also, bacillary DNA present on 454 sputum smears from 223 TB patients were OxyR genotyped and none was recognized as M. bovis. Our data indicate that M. bovis importance on the burden of human TB in Brazil is marginal.


Asunto(s)
Productos Lácteos/microbiología , Mycobacterium bovis/aislamiento & purificación , Tuberculosis/epidemiología , Animales , Brasil/epidemiología , Técnicas de Laboratorio Clínico , Productos Lácteos/efectos adversos , Genotipo , Humanos , Incidencia , Mycobacterium bovis/genética , Vigilancia de la Población , Factores de Riesgo , Tuberculosis/genética , Tuberculosis/transmisión
12.
J Immunol ; 183(1): 718-31, 2009 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-19535630

RESUMEN

Immune mediators associated with human tuberculosis (TB) remain poorly defined. This study quantified levels of lung immune mediator gene expression at the time of diagnosis and during anti-TB treatment using cells obtained by induced sputum. Upon comparison to patients with other infectious lung diseases and volunteers, active pulmonary TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity. Despite the concomitant heightened levels of Th1-type mediators, immune activation may be rendered ineffectual by high levels of intracellular (SOCS and IRAK-M) and extracellular (IL-10 and TGF-betaRII, IL-1Rn, and IDO) immune suppressive mediators. These modulators are a direct response to Mycobacterium tuberculosis as, by day 30 of anti-TB treatment, many suppressive factors declined to that of controls whereas most Th1-type and innate immune mediators rose above pretreatment levels. Challenge of human immune cells with M. tuberculosis in vitro up-regulated these immune modulators as well. The observed low levels of NO synthase-2 produced by alveolar macrophages at TB diagnosis, along with the heightened amounts of suppressive mediators, support the conclusion that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type and innate immunity as an immunopathological strategy. Our data highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.


Asunto(s)
Regulación hacia Abajo/inmunología , Pulmón/inmunología , Pulmón/patología , Células TH1/inmunología , Células TH1/patología , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/patología , Adulto , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/microbiología , Células Cultivadas , Regulación hacia Abajo/genética , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Esputo/inmunología , Esputo/microbiología , Células TH1/microbiología , Tuberculosis Pulmonar/genética , Adulto Joven
13.
J Pediatr (Rio J) ; 85(3): 183-93, 2009.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-19492166

RESUMEN

OBJECTIVES: To present an updated review concerning new assays for diagnosing tuberculosis based on in vitro interferon-gamma production by host T cells, and compare them with tuberculin skin test. METHODS: A literature review was carried out based on Medline and LILACS databases (2000-2008) searching for the following keywords: tuberculosis, interferon-gamma, quantiFERON, ELISPOT and T-SPOT.TB. RESULTS: These new assays proved to have, in general, equal or superior sensitivity and specificity than the tuberculin skin test not only in adults but also in children and immunosuppressed patients for the diagnosis of both latent tuberculosis infection or active disease, with some advantages such as less cross-reactivity as a result of previous BCG vaccination, less influence of anergy and better accuracy in small children. In the United States, these assays have been used instead of the tuberculin skin test and, although still very expensive, the World Health Organization will be making its economic viability a priority. CONCLUSIONS: Always having in mind the importance of clinical and epidemiological histories, these new assays based on interferon-gamma release present promising results and should be considered in tuberculosis investigation procedures for all patients, however with a special concern in the risk groups (i.e., children and immunosuppressed patients).


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Interferón gamma/biosíntesis , Linfocitos T/inmunología , Tuberculosis/diagnóstico , Niño , Humanos , Interferón gamma/sangre , Sensibilidad y Especificidad , Prueba de Tuberculina/métodos
14.
BMC Infect Dis ; 9: 23, 2009 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-19250549

RESUMEN

BACKGROUND: Immune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response. METHODS: Using the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-gamma-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment. RESULTS: 58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034). CONCLUSION: IFN-gamma-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Mycobacterium tuberculosis/inmunología , Linfocitos T/inmunología , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Recuento de Células , Método Doble Ciego , Femenino , Humanos , Interferón gamma/metabolismo , Estudios Longitudinales , Masculino , Valor Predictivo de las Pruebas , Linfocitos T/metabolismo , Resultado del Tratamiento , Tuberculosis Pulmonar/inmunología , Adulto Joven
16.
J Clin Microbiol ; 45(12): 3891-902, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17898156

RESUMEN

The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in approximately 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD(Rio). Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD(Rio) locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD(Rio) strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD(Rio) lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD(Rio) strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD(Rio) strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD(Rio) M. tuberculosis.


Asunto(s)
Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Polimorfismo Genético , Tuberculosis/epidemiología , Tuberculosis/microbiología , Animales , Brasil/epidemiología , Análisis por Conglomerados , Dermatoglifia del ADN , Elementos Transponibles de ADN/genética , ADN Bacteriano/genética , Genotipo , Humanos , Repeticiones de Minisatélite/genética , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/patogenicidad , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Recombinación Genética , Eliminación de Secuencia , Tuberculosis/patología , Tuberculosis/fisiopatología
17.
Microbiology ; 151(Pt 1): 323-32, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15632449

RESUMEN

Pathogenic mycobacteria survive within phagosomes which are thought to represent a nutrient-restricted environment. Divalent cation transporters of the Nramp family in phagosomes and mycobacteria (Mramp) may compete for metals that are crucial for bacterial survival. The elemental concentrations in phagosomes of macrophages infected with wild-type Mycobacterium tuberculosis (M. tuberculosis strain H37Rv) and a M. tuberculosis Mramp knockout mutant (Mramp-KO), derived from a clinical isolate isogenic to the strain MT103, were compared. Time points of 1 and 24 h after infection of mouse peritoneal macrophages (bcg(S)) were compared in both cases. Increased concentrations of P, Ni and Zn and reduced Cl concentration in Mramp-KO after 1 h of infection were observed, compared to M. tuberculosis vacuoles. After 24 h of infection, significant differences in the P, Cl and Zn concentrations were still present. The Mramp-KO phagosome showed a significant increase of P, Ca, Mn, Fe and Zn concentrations between 1 and 24 h after infection, while the concentrations of K and Ni decreased. In the M. tuberculosis vacuole, the Fe concentration showed a similar increase, while the Cl concentration decreased. The fact that the concentration of several divalent cations increased in the Mramp-KO strain suggests that Mramp may have no impact on the import of these divalent cations into the mycobacterium, but may function as a cation efflux pump. The concordant increase of Fe concentrations within M. tuberculosis, as well as within the Mramp-KO vacuoles, implies that Mramp, in contrast to siderophores, might not be important for the attraction of Fe and its retention in phagosomes of unstimulated macrophages.


Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Cationes Bivalentes/metabolismo , Macrófagos Peritoneales/microbiología , Mycobacterium tuberculosis/metabolismo , Fagosomas/metabolismo , Animales , Proteínas de Transporte de Catión/genética , Eliminación de Gen , Humanos , Transporte Iónico , Ratones , Ratones Endogámicos C57BL , Mycobacterium tuberculosis/genética
18.
Mem. Inst. Oswaldo Cruz ; 99(7): 749-752, Nov. 2004. ilus
Artículo en Inglés | LILACS | ID: lil-391606

RESUMEN

Transmission of Mycobacterium bovis from cattle to humans has been reported and can cause tuberculosis (Tb) and a problem in certain risk populations. Therefore, knowledge of resistance of M. bovis towards antibiotics used for therapy of human Tb could help avoiding cure delay and treatment cost increase when dealing with drug resistant organisms. We therefore evaluated the susceptibility of M. bovis isolates towards streptomycin, isoniazide, rifampicin, ethambutol, and ethionamide, the first line antibiotics for human Tb. Therefore, 185 clinical samples from cattle with clinical signs of tuberculosis were processed and submitted to culturing and bacterial isolates to identification and drug susceptibility testing using the proportion method. Among 89 mycobacterial strains, 65 were identified as M. bovis and none were resistant to any of the antibiotics used. Confirmation of present results by future studies, enrolling a large number of isolates and designed to properly represent Brazilian regions, may favor the idea of using isoniazide preventive therapy as part of a Tb control strategy in special situations. Also, nucleic acids from bacterial isolates were submitted to rifoligotyping, a recently described reverse hybridization assay for detection of mutations causing resistance towards rifampicin. Concordance between the conventional and the molecular test was 100 percent, demonstrating the use of such methodology for rapid evaluation of drug susceptibility in M. bovis.


Asunto(s)
Humanos , Animales , Bovinos , Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium bovis , Estudios Retrospectivos
19.
J. bras. pneumol ; 30(4): 388-394, jul.-ago. 2004.
Artículo en Portugués | LILACS | ID: lil-383150

RESUMEN

O ressurgimento da tuberculose como uma das doenças contagiosas que mais assola a humanidade deu-se após uma falsa impressão de que se caminhava para o seu controle antes do final do Século XX. Nos últimos dez anos, em associação com centros de pesquisas norte-americanos e europeus, nosso grupo na Universidade Federal do Rio de Janeiro tem estudado diversos aspectos relacionados com a patogenia da forma pulmonar, a mais importante por conta de sua freqüência e importância que tem no ciclo de transmissão. Nossa hipótese é que o estabelecimento da infecção latente e o desenvolvimento da forma ativa dependem de um desequilíbrio entre citocinas ativadoras e desativadoras da função microbicida dos macrófagos. A despeito da presença de mecanismos habitualmente protetores, como de moléculas nos macrófagos que denotam ativação celular e de moléculas comprometidas com a proteção contra a tuberculose, como o óxido nítrico e o interferon-g, a tuberculose progride. Um dos motivos é a presença no sítio de infecção de moléculas como a interleucina-10 e o TGF-b, que tem capacidade de desativar macrófagos previamente ativados. Existem evidências que a micobactéria secreta proteínas capazes de induzir a expressão de interleucina-10, agindo assim para burlar os mecanismos de defesa. Indivíduos suscetíveis teriam mais capacidade de responder a estas moléculas da micobactéria, devido a mutações genéticas que facilitam a produção de interleucina-10. A compreensão destes mecanismos poderá representar avanços na prevenção e descoberta de novos alvos terapêuticos para o controle da tuberculose.


Asunto(s)
Humanos , Enfermedades Transmisibles Emergentes , Citocinas/inmunología , Tuberculosis Pulmonar/etiología , Tuberculosis Pulmonar/inmunología
20.
Infect Immun ; 72(5): 2628-34, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15102771

RESUMEN

Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor beta (TGF-beta) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-beta receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-gamma) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-gamma, and bioactive TGF-beta were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis.


Asunto(s)
Receptores de Activinas Tipo I/genética , Interleucina-10/biosíntesis , Receptores de Factores de Crecimiento Transformadores beta/genética , Factor de Crecimiento Transformador beta/biosíntesis , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/inmunología , Adulto , Secuencia de Bases , Líquido del Lavado Bronquioalveolar/inmunología , Estudios de Casos y Controles , ADN Complementario/genética , Femenino , Expresión Génica , Humanos , Tolerancia Inmunológica , Interleucina-10/genética , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor Tipo II de Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta/genética
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