Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, India.
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States.
J Biomed Sci. 2020 Jun 17;27(1):74. doi: 10.1186/s12929-020-00667-6.
Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.
由分枝杆菌引起的肺部疾病对人类健康造成了重大的发病率和死亡率。除了由结核分枝杆菌（Mtb）引起的结核病（TB）外，最近的流行病学研究表明，非结核分枝杆菌（NTM）物种的出现也导致了人类肺部疾病。虽然有超过 170 种 NTM 存在于各种环境小生境中，但只有少数几种，主要是鸟分枝杆菌复合体和脓肿分枝杆菌，与肺部疾病有关。虽然 TB 通过吸入含有 Mtb 的气溶胶飞沫传播，这些飞沫是由有症状的患者产生的，但 NTM 病主要通过源自环境的气溶胶传播。然而，在吸入后，Mtb 和 NTM 都被肺泡巨噬细胞吞噬。随后，各种免疫细胞从循环中募集到感染部位，导致肉芽肿形成。尽管 TB 和 NTM 疾病的病理生理学有几个共同的基本细胞和分子事件，但宿主对 Mtb 和 NTM 感染的易感性是不同的。TB 和 NTM 病例的临床表现也存在显著差异。虽然 NTM 病主要与支气管扩张症有关，但这种情况很少是 TB 的诱发因素。同样，在人类免疫缺陷病毒（HIV）感染者中，NTM 病表现为播散性、肺外形式，而不是 Mtb 感染中所见的粟粒性、肺部疾病。与 NTM 感染相比，用于 TB 的诊断方法，包括分子诊断和药物敏感性测试（DST），更先进，具有更高的敏感性和特异性。一般来说，药物敏感的 TB 通过包含明确的一线和二线抗生素的标准多药方案有效治疗。然而，耐药性 TB 的治疗需要在联合或不联合一线和二线药物的情况下使用新的抗生素类别。相比之下，NTM 物种对标准抗 TB 药物的敏感性表现出显著的异质性。因此，NTM 疾病的治疗通常涉及使用大环内酯类和注射用氨基糖苷类药物。尽管有成熟的国际指南，但 NTM 疾病的治疗大多是经验性的，并非完全成功。一般来说，NTM 疾病的治疗时间比 TB 长得多，对于对抗生素治疗无反应的 NTM 疾病患者，切除受影响的器官（s）是治疗的一部分。在这里，我们讨论了人类 TB 和 NTM 疾病的流行病学、诊断和治疗方法。
