【作者】 李蒙； 路丽苹； 江琦； 杨崇广； 郭晓芹； 沈鑫； 高谦；

【Author】 Li Meng;Lu Liping;Jiang Qi;Yang Chongguang;Guo Xiaoqin;Shen Xin;Gao Qian;Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS),School of Basic Medical Science,Shanghai Medical College,Fudan University;Department of Tuberculosis Control,Songjiang District Center for Disease Control and Prevention;Tuberculosis Laboratory,Shanghai Municipal Center for Disease Control and Prevention;

【机构】 复旦大学基础医学院教育部,卫健委、医科院医学分子病毒学重点实验室； 上海市松江区疾病预防控制中心； 上海市疾病预防控制中心结核病实验室；

【摘要】 【目的】流动人口给中国大城市的结核病防控带来巨大挑战。我们旨在通过长期的结核病基因组流行病学研究揭示城市地区结核病的特点和传播规律以及动态变化情况,为制定有效措施进一步降低大城市结核病负担提供理论依据。【方法】2011年1月1日至2020年12月31日,我们在上海市松江区开展了基于人群的前瞻性结核病基因组流行病学研究。对培养阳性的临床菌株进行全基因组测序。当菌株之间的SNP小于等于12,认为菌株基因组成簇,并利用logistic回归分析成簇的风险因素。利用phybreak推断每个基因簇内的传播关系。我们计算了患者之间成对的家庭住址之间的直线距离,并分析与对应患者菌株之间SNP距离的关系。绘制核密度图分析患者的空间分布热点。【结果】研究期间松江共2299例培养阳性肺结核患者,排除菌株复苏失败和比对失败的患者后,有2212例患者及其菌株纳入本研究,其中74.7%(1652/2212)是流动人口。松江区整体成簇率为25.2%(558/2212)。我们以3年的患者为一个样本集,计算了每3年的成簇率,发现研究期间成簇率未发生显著改变。在流动人口患者中仅男性(aOR 1.59,95%CI 1.23-2.06)是成簇的高危人群,而在常住人口患者中年轻人(<25岁:aOR 2.63,95%CI1.11-6.27;25-44岁:aOR 2.40,95%CI 1.23-4.69)和从事体力劳动者(aOR 2.94,95%CI 1.47-5.85)是成簇的高危人群。传播推断表明77.9%(212/272)的传播发生在常住人口患者或流动人口患者内部,仅22.1%(60/272)的传播发生在常住人口患者和流动人口患者之间;进一步分析发现常住人口更容易传播给流动人口:常住人口作为指示病例的76次传播事件中,29次(38.2%)传播给流动人口;流动人口作为指示病例的196次传播事件中,31次(15.5%)传播给常住人口(p<0.001)。空间分析发现,随着患者之间空间距离的增加,成簇风险迅速降低,但超过一半的传播事件发生在居住相聚5公里以上的患者之间。核密度图显示成簇患者与不成簇患者的空间热点基本一致,集中在松江区中部和东部,而且研究期间空间分布没有显著改变。【结论】近期传播是松江区结核病的一个重要来源。随着患者居住空间距离的增加,近期传播的风险迅速降低。近十年,松江区成簇率和患者空间分布均未发生显著变化。目前,上海市结核病防控工作遭遇瓶颈,现行的防控策略可能很难使上海的结核病负担进一步下降。因此,迫切需要新的策略,加强患者发现,阻断结核病的传播,达到降低疫情的目的。更多还原

【Abstract】 Objective:The internal migrants pose a great challenge to the tuberculosis(TB) control in China.We aimed to describe the characteristics,transmission patterns,and dynamic changes of TB in an urban setting.Methods:We conducted a population-based study of culture-positive pulmonary TB patients diagnosed between January 1,2011 and December 31,2020 in Songjiang,Shanghai.Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms,based on whole-genome sequencing.Risk factors for clustering were identified by logistic regression.Transmission inference was performed using R package phybreak.We calculated the pairwise distances between the residences and compared these to the genomic distances.Kernel density estimation was used to analyze the spatial hotspots of patients.Results:Of the 2212 enrolled patients,74.7%(1652/2212) were internal migrants.The clustering rate was 25.2%(558/2212) during the study period and we also calculated the clustering rate using patients every 3 years as a dataset and found no significant changes.Among migrant patients,only males(aOR 1.59,95% CI 1.23-2.06) had a greater risk of clustering,whereas among resident patients,patients who were young(<25 years:aOR 2.63,95% CI 1.11-6.27;25-44 years:aOR 2.40,95% CI 1.23-4.69) or engaged in physical labor(aOR 2.94,95% CI 1.47-5.85) had a greater risk of clustering.Transmission inference showed that 77.9%(212/272) of the transmission events occurred between either resident patients or migrant patients,and only 22.1%(60/272) occurred between resident and migrant patients;further analysis showed that residents were more likely to transmit to migrants than migrants were to residents:29(38.2%) of 76 transmission events initiated by a resident resulted in a secondary case in a migrant,and 31(15.8%) of 196 transmission events initiated by a migrant resulted in a secondary case in a resident(p<0.001).Spatial analysis found that the risk for clustering decreased rapidly with increasing distances between the residences.However,more than half of clustered patients were located ≥5 kilometers apart.The spatial hotspots of clustered and unclustered patients didn’t change significantly during the study period.Conclusion:Recent transmission was an important driver of TB infection in Songjiang.The risk for genomic clustering decreased rapidly with increasing geographical distances between the residences.Neither the clustering rate nor the spatial hotspots of TB patients has changed significantly in the last decade.The current TB prevention and control strategies may make it difficult to further reduce the TB burden in Shanghai.Therefore,new strategies are urgently needed to enhance patient detection,interrupt TB transmission,and achieve a reduction in the epidemic.更多还原