Laughon Barbara E
Complications and Co-Infections Research Branch, Therapeutics Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-7624, USA.
Curr Top Med Chem. 2007;7(5):463-73. doi: 10.2174/156802607780059736.
Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more. About one third of the world's population is silently infected with TB that may erupt into disease with increased age or suppression of the immune system. Nearly nine million new active cases develop every year. The World Health Organization (WHO) declared the disease a global emergency as long ago as 1993. Although huge efforts in public health control have reduced the disease burden within most established market economies, in Africa and Asia the epidemic continues to accelerate, particularly fueled by the HIV epidemic. Furthermore, resistance to the standard drugs isoniazid and rifampicin is increasing worldwide. Since the 1990s, mycobacteria have emerged with resistance patterns rendering all currently available antibiotics ineffectual. The pharmaceutical industry has mostly abandoned TB drug development due to perceived non-profitable consumer market and the diminishing number of companies engaged in anti-infective research. The public sector and infectious disease researchers have responded to advance fundamental science and to create new chemical entities as early drug candidates. With support from research funding agencies, philanthropic donors, and the STOP-TB Partnership, new chemical tools and new approaches to effectively implement TB control programs are evolving. Advanced preclinical development and strategies for Phase III clinical trials remain gap areas that will require additional engagement from all sectors.
在过去的50年里，没有新的药物类别被用于治疗结核病。结核病每年导致近200万人死亡，主要集中在发展中世界最贫困的社区。还有数百万人受到感染。世界上约三分之一的人口被结核菌隐性感染，这种感染可能会随着年龄增长或免疫系统受到抑制而引发疾病。每年新增近900万活动性病例。早在1993年，世界卫生组织（WHO）就宣布该病为全球紧急情况。尽管在公共卫生控制方面付出了巨大努力，大多数发达市场经济体的疾病负担有所减轻，但在非洲和亚洲，疫情仍在加速蔓延，尤其是在艾滋病疫情的推动下。此外，全球范围内对标准药物异烟肼和利福平的耐药性正在增加。自20世纪90年代以来，出现了一些耐药模式的分枝杆菌，使目前所有可用的抗生素都失效。由于认为消费者市场无利可图，以及从事抗感染研究的公司数量不断减少，制药行业大多放弃了结核病药物研发。公共部门和传染病研究人员已做出回应，推进基础科学研究，并创造新的化学实体作为早期候选药物。在研究资助机构、慈善捐赠者和遏制结核病伙伴关系的支持下，有效实施结核病控制项目的新化学工具和新方法正在不断发展。临床前的高级开发和三期临床试验策略仍然是空白领域，需要所有部门进一步参与。
