RESUMEN
Lungs are the central organ affected and targeted by Mycobacterium tuberculosis and immune processes in the lung are of critical importance in the pathogenesis of tuberculosis. A major lung defense against invading pathogens is provided by surfactant protein A, a multi-chain protein encoded by the SFTPA1 and SFTPA2 genes. Here, we investigated polymorphisms in the SFTPA1 and SFTPA2 genes for association with tuberculosis in 181 Ethiopian families comprising 226 tuberculosis cases. Four polymorphisms, SFTPA1 307A, SFTPA1 776T, SFTPA2 355C, and SFTPA2 751C, were associated with tuberculosis (P=0.00008; P=0.019, P=0.029 and P=0.042, respectively). Additional subgroup analysis in male, female and more severely affected patients provided evidence for SFTPA1/2-covariate interaction. Finally, out of five intragenic haplotypes identified in the SFTPA1 gene and nine identified in the SFTPA2 gene, 1A(3) was most significantly associated with tuberculosis susceptibility (P=0.026). These findings suggest that SFTPA1 and SFTPA2 modify the risk of tuberculosis susceptibility and that this risk is influenced by additional covariates.
Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo Genético , Proteína A Asociada a Surfactante Pulmonar/genética , Tuberculosis/genética , Adolescente , Adulto , Niño , Progresión de la Enfermedad , Etiopía , Familia , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Humanos , MasculinoRESUMEN
BACKGROUND: In many settings, the diagnosis of pulmonary tuberculosis depends on sputum microscopy. However, this technique has low sensitivity. We studied the efficacy and safety of sputum digestion with bleach prior to Ziehl-Neelsen (ZN) staining. METHODS: Positive sputum smears were assessed for staining quality and viability of mycobacteria after varying bleaching times. Two hundred smears were then prepared from the first, second and third sputum sample of tuberculosis suspects. Equal amounts of 5% bleach were added to the remaining first sputum and ZN smears were prepared. FINDINGS: Optimal quality and staining was achieved with 30-45 min of bleaching. No growth was observed from positive samples after 15 min. Bleached specimens had 26% (52/200) positivity compared to 17.5% (35/ 200) of unbleached smears (P < 0.001). The bleached smears had 92.3% sensitivity, 93.4% specificity, 78.3% and 97.7% positive and negative predictive values, respectively, against a case definition. Ten patients failed to submit a second or third sputum. Six patients were positive on either the standard or bleach-digested smears, or both. INTERPRETATION: Bleach digestion is simple, cheap and kills mycobacteria. Its positivity rate is as good as three standard smears. This method has the potential to improve over-burdened services in developing countries.