RESUMO
Resumen La tuberculosis es un problema de salud mundial exacerbado por la ausencia de una vacuna eficaz y la emergencia de cepas multidrogo resistentes. La inmunidad innata, clave en la susceptibilidad a tuberculosis, está asociada a polimorfismos genéticos en TLRs (Toll Like Receptors), VDR (Vitamin D Receptor), INF-γ, TNF-α, entre otros. Recientemente, también a nueve genes causantes de susceptibilidad mendeliana a enfermedades micobacterianas (MSMD), incluyendo genes autosómicos y ligados al cromosoma X. Después de décadas de exitoso manejo, Chile reportó mantención de la mortalidad, aumento en la incidencia de tuberculosis en todas sus formas y casos multidrogo resistentes. La incidencia es mayor en Norte y Centro, donde la Región Metropolitana mostró incremento de población migrante latinoamericana. Consecuentemente, la alta persistencia de la incidencia en tales zonas geográficas, podría asociarse a poblaciones portadoras de polimorfismos de un solo nucleótido (SNP)s y/o MSMD, confiriendo susceptibilidad genética a tuberculosis y/o a BCG diseminada y otros patógenos intramacrofágicos, similar a lo descrito en poblaciones de Europa, Asia, África y América. En conclusión, proponemos considerar la predisposición genética de la población actual, al momento de diseñar políticas nacionales de salud pública para erradicar la tuberculosis.
Tuberculosis is a global health problem exacerbated by the absence of an effective vaccine and emergence of extensive antibiotic-resistant strains. Innate immunity is key to tuberculosis susceptibility, since it is associated with genetic polymorphisms in TLRs (Toll Like Receptors), VDR (Vitamin D Receptor), INF-γ, TNF-α, among others. Recently, also to nine Mendelian Susceptibility Mycobacterial Diseases (MSMD) -causing genes, including autosomal and X-linked genes. After decades of successful management, Chile reported maintenance of mortality and increase in tuberculosis under 15 years and multidrug resistant cases incidence. Moreover, incidence is higher in the North and the Center, where Metropolitan Region showed a sustained increment of the Latin American migrant population. Consequently, the high incidence persistence in such geographic areas could be associated with populations carrying SNPs genetic polymorphisms types and/or MSMD that confer genetic susceptibility to tuberculosis and/or BCG dissemination and other intramacrophagic pathogens, similar to that described in certain populations in Europe, Asia, Africa and America. Corollary, we propose to consider genetic predisposition of the current population, at the time of designing national public health policies to eradicate tuberculosis.
Assuntos
Humanos , Tuberculose/genética , Tuberculose/imunologia , Polimorfismo Genético , Predisposição Genética para Doença , Genótipo , Imunidade InataRESUMO
Mycobacterium tuberculosis, the etiological agent of human tuberculosis, causes annually three million deaths and latently infects about two billion people. Immunodeficiency caused by malnutrition, senescence or co-infection with HIVenhances the risk of developing active tuberculosis, either from a primary infection or by reactivation of a latent infection. The increasing appearance of multidrug-resistant strains to existing drugs is worrisome, since it leaves patients practically without treatment options. The understanding of the mechanisms of transmission, pathogenesis and virulence of M. tuberculosis is important. The analysis of its genome shows the presence of alternative sigma factors, transcriptional repressors and activators, two component signaling systems, metabolic enzymes and cellular secretory systems, that are associated with virulence in a series of pathogenic micro-organisms. Environmental stimuli such as pH, temperature, osmolality, oxygen availability are processed, activating or repressing virulence genes. The molecular mechanisms of action of these genes have been elucidated in in vitro and in vivo models.