Smith Issar
TB Center, Public Health Research Institute, International Center for Public Health, Newark, New Jersey 07103-3535, USA.
Clin Microbiol Rev. 2003 Jul;16(3):463-96. doi: 10.1128/CMR.16.3.463-496.2003.
Tuberculosis (TB), one of the oldest known human diseases. is still is one of the major causes of mortality, since two million people die each year from this malady. TB has many manifestations, affecting bone, the central nervous system, and many other organ systems, but it is primarily a pulmonary disease that is initiated by the deposition of Mycobacterium tuberculosis, contained in aerosol droplets, onto lung alveolar surfaces. From this point, the progression of the disease can have several outcomes, determined largely by the response of the host immune system. The efficacy of this response is affected by intrinsic factors such as the genetics of the immune system as well as extrinsic factors, e.g., insults to the immune system and the nutritional and physiological state of the host. In addition, the pathogen may play a role in disease progression since some M. tuberculosis strains are reportedly more virulent than others, as defined by increased transmissibility as well as being associated with higher morbidity and mortality in infected individuals. Despite the widespread use of an attenuated live vaccine and several antibiotics, there is more TB than ever before, requiring new vaccines and drugs and more specific and rapid diagnostics. Researchers are utilizing information obtained from the complete sequence of the M. tuberculosis genome and from new genetic and physiological methods to identify targets in M. tuberculosis that will aid in the development of these sorely needed antitubercular agents.
结核病是已知最古老的人类疾病之一，至今仍是主要的致死原因之一，每年有两百万人死于这种疾病。结核病有多种表现形式，可影响骨骼、中枢神经系统和许多其他器官系统，但它主要是一种肺部疾病，由气溶胶飞沫中所含的结核分枝杆菌沉积在肺泡表面引发。从这一点来看，疾病的进展可能有几种结果，这在很大程度上取决于宿主免疫系统的反应。这种反应的效果受内在因素影响，如免疫系统的遗传学因素，以及外在因素，如对免疫系统的损害和宿主的营养及生理状态。此外，病原体可能在疾病进展中起作用，因为据报道，一些结核分枝杆菌菌株比其他菌株更具毒性，其定义为传播性增加以及与感染个体的更高发病率和死亡率相关。尽管减毒活疫苗和几种抗生素已广泛使用，但结核病的病例比以往任何时候都多，这需要新的疫苗、药物以及更特异、快速的诊断方法。研究人员正在利用从结核分枝杆菌基因组全序列以及新的遗传和生理学方法中获得的信息，来确定结核分枝杆菌中的靶点，这将有助于开发这些急需的抗结核药物。
