Nebenzahl-Guimaraes Hanna, Verhagen Lilly M, Borgdorff Martien W, van Soolingen Dick
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal ICVS/3Bs, PT Government Associate Laboratory, Braga/Guimarães, Portugal
Wilhelmina Children's Hospital Utrecht, Utrecht, The Netherlands Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
J Clin Microbiol. 2015 Oct;53(10):3264-71. doi: 10.1128/JCM.01370-15. Epub 2015 Jul 29.
The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.
本研究的目的是确定分枝杆菌谱系是否会影响荷兰结核分枝杆菌病例的感染风险、聚集性和疾病进展。使用针对患者相关因素进行调整并按患者种族分层的多变量负二项回归模型，来确定系统发育谱系与传染性（每位患者周围阳性接触者的平均数量）和聚集性（根据索引病例诊断后2年内具有相同指纹的二代病例数量定义）指标之间的关联。通过将聚集性指数与传染性指数进行自展风险比计算，得出每个风险因素导致疾病进展的估计值。与欧美参照组相比，非洲分枝杆菌在外国出生人群中的传染性和聚集性指数显著较低，而牛分枝杆菌在本国人群中的传染性和聚集性指数显著较低。在外国出生人群中，东非印度谱系的传染性也显著较低。涂片阳性是传染性增加和聚集性增加的重要风险因素。疾病进展的估计值与年龄、痰涂片状况以及行为风险因素（如酗酒和静脉注射药物滥用）显著相关，但与系统发育谱系无关。总之，我们发现有证据表明存在一个影响菌株传播指标的细菌学因素，即与现代谱系相比，古老系统发育谱系的感染能力下降且聚集性指数较低。通过使用结核菌素皮肤试验转阳数据的随访研究来证实这些发现，应该会对结核分枝杆菌的控制工作产生重要影响。
