Lange Christoph, Mandalakas Anna M, Kalsdorf Barbara, Denkinger Claudia M, Sester Martina
Division of Clinical Infectious Diseases, Medical Clinic Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), Clinical Tuberculosis Center, Borstel, Germany; International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Internal Medicine, University of Namibia School of Medicine, Windhoek, Namibia.
Global Tuberculosis Program, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States.
Pathog Immun. 2016;1(2):308-329. doi: 10.20411/pai.v1i2.173. Epub 2016 Jan 4.
Despite global efforts to control tuberculosis (TB) the estimated number of people who developed TB worldwide increased to an all-time record of more than 10 million in 2015. The goal of the World Health Organization (WHO) to reduce the global incidence of TB to less than 100 cases per million by 2035, cannot be reached unless TB prevention is markedly improved. There is a need for an improved vaccine that better protects individuals who are exposed to from infection and active disease compared to the current Bacille Calmette Guérin (BCG) vaccine. In the absence of such a vaccine, prevention relies on infection control measures and preventive chemotherapy for people with latent infection with (LTBI), who have the highest risk of progression to active TB. During the past decade, interferon-γ release assays (IGRAs) have increasingly replaced the tuberculin skin test as screening tools for the diagnosis of LTBI in countries with a low incidence of TB. Despite recent WHO guidelines on the management of LTBI, the definition of groups at risk for TB remains controversial, and the role of IGRAs for TB prevention in low-incidence countries remains uncertain. We reviewed the scientific literature and provide recommendations for the use of IGRAs for LTBI diagnosis in low-incidence countries. These recommendations are based on the number of patients needing treatment in order to prevent one case of TB. As the positive predictive value of IGRAs for the development of TB is sub-optimal, research must focus on the identification of alternative biomarkers that offer better predictive ability in order to substantially reduce the number needing treatment while improving the prevention of TB and improving the effectiveness of targeted preventive chemotherapy.
尽管全球为控制结核病做出了努力，但2015年全球结核病发病人数估计增至1000多万，创历史新高。世界卫生组织（WHO）提出到2035年将全球结核病发病率降至每百万人口低于100例的目标，除非结核病预防工作得到显著改善，否则无法实现。需要一种改进型疫苗，与目前的卡介苗（BCG）相比，能更好地保护接触结核菌的个体免受感染和患活动性疾病。在没有这种疫苗的情况下，预防工作依赖于感染控制措施以及对潜伏性结核感染（LTBI）人群进行预防性化疗，这些人发展为活动性结核病的风险最高。在过去十年中，在结核病发病率较低的国家，干扰素-γ释放试验（IGRAs）已越来越多地取代结核菌素皮肤试验，作为诊断LTBI的筛查工具。尽管WHO最近发布了关于LTBI管理的指南，但结核病高危人群的定义仍存在争议，IGRAs在低发病率国家结核病预防中的作用也仍不确定。我们回顾了科学文献，并就IGRAs在低发病率国家LTBI诊断中的应用提出建议。这些建议基于为预防一例结核病所需治疗的患者数量。由于IGRAs对结核病发生的阳性预测值并不理想，研究必须聚焦于识别具有更好预测能力的替代生物标志物，以便在改善结核病预防和提高针对性预防性化疗效果的同时，大幅减少需要治疗的人数。
