Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population.

BACKGROUND: The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. METHODS: We carried out a case-control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. RESULTS: We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. CONCLUSIONS: Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians.

Risk factors for idiopathic pulmonary fibrosis in a Mexican population. A case-control study.

The etiology of idiopathic pulmonary fibrosis (IPF) remains poorly understood, but some studies have suggested that cigarette smoking or other occupational or environmental exposures, diabetes mellitus, or gastroesophageal reflux may play a role. In this study we evaluated the clinical records of a group of 97 consecutive patients with IPF, and 560 patients suffering 5 different respiratory disorders that were examined as controls: asthma (n=111), chronic obstructive pulmonary disease (n=132), squamous cell lung carcinoma (n=118), lung adenocarcinoma (n=101) and patients with otorhinolaryngology problems but without lung disease (n=98). In bivariate analyses male sex, diabetes mellitus and being former cigarette smoker were associated with IPF. After adjusting by these variables, multivariate analysis revealed that type 2 diabetes mellitus [11.3% in IPF patients vs 2.9% in controls, OR=4.3 (95% CI: 1.9-9.8), p<0.0001] was an independent risk factor associated to IPF. Our results provide additional evidence of a putative relationship between DM2 and idiopathic pulmonary fibrosis. Experimental research is necessary for thorough assessment of the pathogenic mechanisms involved in this association.

Implicaciones de los polimorfismos de un solo nucleótido en Mycobacterium tuberculosis y humanos en el manejo clínico de la tuberculosis / Implication of single nucleotide polymorphisms in Mycobacterium tuberculosis and humans in the clinical management of tuberculosis

Se analizan estudios de los polimorfismos genéticos de Mycobacterium tuberculosis asociados a resistencia y transmisión, así como los polimorfismos genéticos en humanos con asociación a gravedad y formas clínicas de la enfermedad y toxicidad hepática al tratamiento antituberculosis, y su utilidad en el estudio de los pacientes con tuberculosis multifarmacorresistente. Los nuevos métodos que ofrece la medicina geómica para la investigación en tuberculosis permiten sugerir nuevos criterios de aplicación inmediata en el manejo clínico de los pacientes con tuberculosis, en la evaluación de la eficacia de la terapéutica y en la prevención de eventos adversos para el paciente. Por ello, es importante evaluar el costo-beneficio de esta herramienta para fortalecer los centros de atención a pacientes con tuberculosis en países en desarrollo donde existen elevadas tasas de la enfermedad.

We review studies of Mycobacterium tuberculosis genetic polymorphisms associated to resistance and transmission; also, the genetic polymorphisms associated to severity and clinical presentation of human tuberculosis (TB) and hepatic toxicity associated to antituberculosis treatment. We discuss its usefulness in studies of patients with multidrug resistant TB. The new methods of genomic medicine suggest new criteria for immediate application in TB management, the evaluation of treatment efficacy and the prevention of patient complications. It is important to appraise cost-benefit of this tool to improve TB medical care centers from developing countries with high rates of TB.

Respuesta al tratamiento antituberculosis en pacientes con historia de tratamientos previos en el Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas / Response to antituberculous therapy in patients previously treated for TB at the National Institue for Respiratory Diseases Ismael Cosío Villegas

Antecedentes y objetivos: El Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), como centro de referencia nacional de enfermedades respiratorias, recibe pacientes con tuberculosis pulmonar (TBp) que ya han recibido múltiples tratamientos. El objetivo de este estudio fue evaluar los resultados del tratamiento antituberculosis en pacientes previamente tratados que fueron supervisados por el INER durante un nuevo retratamiento. Métodos: Estudio retrospectivo con análisis de los expedientes clínicos mediante un cuestionario estandarizado de los pacientes con TBp con antecedente de tratamiento previo, y cuyo nuevo tratamiento fue supervisado en el INER de 1994-2001. La respuesta al tratamiento fue analizada de acuerdo al número de tratamientos previos, al antecedente de fracaso al tratamiento antes de ingresar al INER, y de acuerdo a la presencia o no de tuberculosis multifarma-corresistente (TB-MFR). Resultados: Se incluyeron a 147 pacientes diagnosticados con TBp que habían recibido tratamiento previo. Las tasas de curación en el INER para los pacientes con uno, dos y tres o más tratamientos previos fueron 68.2%, 40.4%, 8.8% (p = 0.009); de abandono 6.8%, 4.3%, 3.1% (p = 0.7) y de fracaso 18.2%, 27.7%, 25.0% (p = 0.6) para cada uno de los grupos, respectivamente. La proporción de TB-MFR fue de 64.4% 86.3% y 94.4% en cada grupo (x² de tendencia, p = 0.0004). El fracaso previo fue predictor independiente de fracaso actual [RM = 2.4 (IC95% 0.9-6.4) p = 0.04]. Las tasas de curación de acuerdo al patrón de resistencia fueron: monorresistencia 71.4%; multifarmaco-rresistencia 44.9% y polirresistencia 30.8%, (x² de tendencia, p = -03). Conclusiones: En pacientes con TBp con múltiples tratamientos previos y que recibieron un retratamiento supervisado por el INER, hubo bajas tasas de curación, una proporción persistente de fracasos al tratamiento y una alta tasa de TB-MFR.

Background: The National Institute of Respiratory Diseases Ismael Cosío Villegas (INER) is a national third level referral center for all respiratory diseases, including multitreaded pulmonary tuberculosis patients (PTb). The purpose of this study was to evaluate the results of supervised PTb retreatment at the INER in patients previously treated for PTb. Methods: Retrospective review of clinical charts by a standardized questionary of previous treated PTb patients and whose new treatment was given and supervised al the INER from 1994 to 2001. The response was analyzed according to the number of previous treatments, history of failure to previous treatments and presence or absence of MDR PTb. Results: One hundred and forty seven patients had previously received treatment for PTb. The cure rates for patients with one, two, three or more previous PTb treatments were 68.2%, 40.4%, and 8.8% (p = 0.009); desertion 6.8%, 4.3%, and 3.1% (p = 0.7); failure 18.2%, 27.7%, and 25 % (p = 0.6) for each one of the groups, respectively. The proportion of MDR- PTb was 64.4%, 86.3%, and 94.4% in each group (X² trend, p = 0.0004). A previous treatment failure was a predictor of failure of treatment at the INER [OR = 2.4 (CI95% 0.9-9.64), p = 0.04]. According to resistance, cure rates were 71.4% for one drug resistance, MDR 44.9% and poly resistance 30.8% (X² trend, p= -03). Conclusions: For patients with one or more failed previous treatments for PTb, receiving a new supervised treatment regime at the INER, there were low cure rates, a high proportion of treatment failures and a high rate of MDR-PTb.

Motivos de hospitalización en pacientes con tuberculosis pulmonar en un hospital de referencia / Reasons for medical admission in patients with pulmonary tuberculosis in a referral institute

Objetivo: Determinar la prevaíencia de complicaciones torácicas en pacientes con tuberculosis pulmonar hospitalizados en el Instituto Nacional de Enfermedades Respiratorias (INER). Lugar del estudio: INER, centro de tercer nivel y referencia dedicado a la atención médica especializada, docencia e investigación de enfermedades respiratorias. Material y métodos: Se realizó un estudio retrospectivo con la revisión de los expedientes clínicos de pacientes con tuberculosis pulmonar ingresados al INER, en un período que comprendió del 1 de julio al 31 de diciembre de 2003. Resultados: De los 124 pacientes con tuberculosis pulmonar que acudieron al INER durante el período de estudio, 62.9% (78/124) fueron hospitalizados; 44.9% (35/78) del sexo masculino; mediana de edad, 44.5 años (rango 16-78); el diagnóstico bacteriológico se hizo por baciloscopía en 51.3% (40/78); sólo por cultivo, 5.1% (4/78) y por baciloscopía y cultivo, 43.6% (34/78). Del total de pacientes, 66.6% (52/78) se clasificaron en la categoría I de la Organización Mundial de la Salud. La prevaíencia de diabetes mellitus fue 43.7% (31/78). Los motivos de hospitalización fueron: 46.2% (36/78) para diagnóstico; hemoptisis, 34.6% (27/78); infecciones, 5.2% (4/78) y otros motivos, 14.0% (11/78). Presentaron bronquiectasias, 85.7% (66/78); neumonía, 6.4% (5/78); neumonía por Mycobacterium tuberculosis, 5.1% (4/78); empierna, 5.1% (4/78); fístula broncopleural, 3.9% (3/78); aspergiloma, 2.6% (2/78); compresión tráqueo-bronquial, 1.3% (l/78) y fibrotórax, 12.8% (10/78). Conclusiones: Los pacientes hospitalizados en el INER por tuberculosis pulmonar manifestaron una elevada frecuencia de complicaciones, especialmente de bronquiectasias y hemoptisis. Casi 44% de los pacientes presentó diabetes mellitus; uno de cada dos fue hospitalizado para diagnóstico.

Purpose: To determine the prevalence of thoracic complications in hospitalized patients with pulmonary tuberculosis. Setting: National referral hospital for the care, teaching and investigation of respiratory diseases. Material and methods: This study is based on the retrospective analysis of pulmonary tuberculosis patients admitted from July 1 to December 31, 2003 and was conducted at The National Institute of Respiratory Diseases (INER), Mexico. Results: Seventy eight patients with pulmonary tuberculosis were included in the six month period; 35 (44.9%) were male; the bacteriological diagnosis was done by sputum smear in 51.3% (40/78), culture in 5.1% (4/78) and sputum smear and culture in 43.6% (34/78). Patients were classified as WHO category I in 66.7% (52/78); 43.7% had diabetes mellitus (31/78). Admission causes: for diagnosis in 46.2% (36/78); hemoptysis in 34.6% (27/78); infection in 5.2% (4/78); other causes in 14.0% (11/78); bronchiectasis were present in 85.7% (66/ 77); pneumonia in 6.4% (5/78); Mycobacterium tuberculosis pneumonia in 5.1% (4/78); empyema in 5.1% (4/78); bronchopleural fistula in 3.9% (3/ 78); aspergilloma in 2.6% (2/78); tracheobronchial obstruction in 1.3% (1/78); fibrothorax in 12.8% (10/78). Conclusions: Hospitalized pulmonary tuberculosis patients show an elevated rate of pulmonary complications. Almost half had diabetes mellitus; almost half were hospitalized for diagnosis.