Specialty Care, Pfizer, Groton, CT, USA.
Lancet Infect Dis. 2013 Apr;13(4):362-72. doi: 10.1016/S1473-3099(13)70034-3. Epub 2013 Mar 24.
Biomarkers are indispensable to the development of new tuberculosis therapeutics and vaccines. The most robust biomarkers measure factors that are essential to the underlying pathological process of the disease being treated, and thus can capture the full effects of many types of interventions on clinical outcomes in multiple prospective, randomised clinical trials. Many Mycobacterium tuberculosis and human biomarkers have been studied over the past decade. Present research focuses on three areas: biomarkers predicting treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses by vaccination. Many older, non-specific markers of inflammation, when considered in isolation, do not have sufficient predictive values for clinical use in tuberculosis. Although no new accurate, tuberculosis-specific biomarkers have yet been discovered, substantial progress has been made in some areas. However, the qualification of biomarkers as a surrogate for a clinical endpoint in tuberculosis is very challenging, and, for biomarkers that are non-culture-based, impossible to pursue without the availability of well characterised biobanks containing biospecimens from patients who have had adequate follow-up to establish long-term treatment outcome. We review progress in tuberculosis biomarker development and efforts being made to harness resources to meet future challenges.
生物标志物对于新的结核病治疗方法和疫苗的开发至关重要。最可靠的生物标志物衡量的是对所治疗疾病的潜在病理过程至关重要的因素，因此可以在多个前瞻性、随机临床试验中捕捉到许多类型干预措施对临床结果的全面影响。在过去的十年中，已经研究了许多结核分枝杆菌和人类生物标志物。目前的研究集中在三个领域：预测结核病治疗效果和治愈的生物标志物、潜伏性结核感染的再激活、以及疫苗诱导保护性免疫反应。许多较旧的、非特异性炎症标志物，如果单独考虑，对于结核病的临床应用没有足够的预测价值。虽然尚未发现新的准确的结核病特异性生物标志物，但在某些领域已经取得了实质性进展。然而，将生物标志物作为结核病临床终点的替代指标是非常具有挑战性的，对于非培养为基础的生物标志物来说，如果没有包含有充分随访的患者生物标本的特征良好的生物库，就不可能进行研究，以确定长期的治疗结果。我们回顾了结核病生物标志物开发的进展以及为应对未来挑战而做出的努力。
