Center for Clinical Microbiology, Division of Infection and Immunity, University College London (UCL) and NIHR Biomedical Research Centre, UCLHospitals NHS Foundation Trust, United Kingdom.
Therapeutic Immunology, Departments of Laboratory Medicine and Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden.
Clin Infect Dis. 2015 Nov 1;61(9):1432-8. doi: 10.1093/cid/civ631. Epub 2015 Jul 28.
Tuberculosis remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of tuberculosis treatment has been on antibiotic development targeting Mycobacterium tuberculosis. The lengthy tuberculosis treatment duration and poor treatment outcomes associated with multi-drug resistant tuberculosis (MDR-TB) are of major concern. The sparse new tuberculosis drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the "microbe" vs the "host internal milieu" in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of tuberculosis therapy and improving treatment outcomes for drug-susceptible tuberculosis and MDR-TB. Funder initiatives that may enable further research into HDTs are described.
结核病仍然是一个全球性的紧急问题，每年估计导致 150 万人死亡。几十年来，结核病治疗的主要重点一直是针对结核分枝杆菌的抗生素开发。结核病治疗时间长，以及耐多药结核病（MDR-TB）相关的治疗效果不佳，令人严重关切。结核病新药物研发管道稀疏，MDR-TB 广泛出现，表明迫切需要更多创新干预措施来改善治疗效果。借鉴历史上巴斯德-贝尚论战中关于“微生物”与“宿主内部环境”在疾病病因中的作用，我们提出了对宿主定向治疗（HDT）进行平行投资的理由。现在有一系列潜在的 HDT 可用，需要在随机对照临床试验中作为辅助治疗进行评估，以缩短结核病治疗时间并改善对药物敏感结核病和 MDR-TB 的治疗效果。描述了可能使 HDT 进一步研究成为可能的资助倡议。
