Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure
Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure
复制标题
DOI：
10.1038/nm.4177
复制
发表时间：
2016-10-01
期刊：
影响因子：
82.9
通讯作者：
Walzl, Gerhard
中科院分区：
文献类型：
--
作者：
Malherbe, Stephanus T.;Shenai, Shubhada;Walzl, Gerhard
缺乏一个金标准来确定抗生素何时产生灭菌治愈，这扰乱了治疗肺结核(PTB)的新方法的发展。我们检测到与活动性疾病相一致的正电子发射断层扫描和计算机断层扫描(PET-CT)成像反应模式，以及痰和支气管肺泡灌洗样本中结核分枝杆菌(MTB)mRNA的存在，在相当大比例的成年、HIV阴性的肺结核患者中，经过标准的6个月治疗和1年随访，包括持久治愈的患者和其他后来出现复发的患者。在PET-CT图像上未溶解和加重的病变中存在MTB mRNA可能表明正在进行转录，这表明即使是表面上治愈的肺结核治疗也不能根除大多数患者中的所有MTB细菌。这表明免疫反应在维持无疾病状态方面起着重要的补充作用。消毒药物或宿主导向疗法，以及更好的治疗反应标记物，可能是成功开发改进和缩短的肺结核治疗策略所必需的。
The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.