Assessment of Mycobacterium tuberculosis transmission in Oxfordshire, UK, 2007-12, with whole pathogen genome sequences: an observational study.
Assessment of Mycobacterium tuberculosis transmission in Oxfordshire, UK, 2007-12, with whole pathogen genome sequences: an observational study.
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DOI：
10.1016/s2213-2600(14)70027-x
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发表时间：
2014-04
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影响因子：
--
通讯作者：
Conlon CP
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作者：
Walker TM;Lalor MK;Broda A;Ortega LS;Morgan M;Parker L;Churchill S;Bennett K;Golubchik T;Giess AP;Del Ojo Elias C;Jeffery KJ;Bowler ICJW;Laurenson IF;Barrett A;Drobniewski F;McCarthy ND;Anderson LF;Abubakar I;Thomas HL;Monk P;Smith EG;Walker AS;Crook DW;Peto TEA;Conlon CP
自 2000 年以来，英国境外出生的患者导致英国结核病发病率上升 20%，但他们对国内传播的影响尚不清楚。在这里，我们使用全基因组测序来调查六年来未经选择的人群中结核病传播的流行病学。我们使用当地数据库并对照国家强化结核病监测数据库进行核对，确定了 2007 年 1 月 1 日至 2012 年 12 月 31 日期间具有结核分枝杆菌培养或临床诊断为结核病的所有牛津郡邮政编码的居民。我们使用 Illumina 技术对已识别病例中所有可用的结核分枝杆菌培养物进行测序。序列根据遗传相关性进行聚类，并与接触调查进行回顾性比较。每个集群中诊断的第一例患者被定义为指示病例，首先通过使用任何流行病学联系，然后通过遗传距离，然后通过诊断时间分配与后续病例的链接。尽管我们确定了 384 名被诊断患有结核病的患者，但其中 380 名患者的出生国家是已知的，而且我们对 269 例经培养确诊的疾病病例中的 247 例进行了分离株测序。 13 个簇内有 39 例基因组连锁，这意味着 26 起本地传播事件。之前通过接触者追踪仅发现了 26 种可能的传播中的 11 种。在七个经基因组确认的家庭簇中，五个包含与流行病学上未识别的非家庭成员的额外基因组联系。 255 名 (67%) 患者出生在结核病高发国家，牛津郡的当地发病率为每年每 10 万人口 109 例，而出生在低发病率国家的患者每年每 10 万人口 3·5 例。然而，出生在低发病率国家（主要是英国）的患者更有可能患有肺部疾病（调整后比值比 1·8 [95% CI 1·2–2·9]；p=0·009）、社会危险因素（4·4 [2·0–9·4]；p<0·0001），并且属于本地传播集群的一部分（4·8 [1·6–14·8]； p=0·006）。尽管向内移民导致了结核病的总体发病率，但我们的研究结果表明，大多数出生在高发国家的患者会重新激活在国外获得的潜伏感染，并且不参与当地的进一步传播。对新进入者进行系统筛查可以进一步改善结核病控制，但重要的是，如果不想危及结核病控制，那么所有人，特别是高危人群仍然可以获得医疗保健。
Patients born outside the UK have contributed to a 20% rise in the UK’s tuberculosis incidence since 2000, but their effect on domestic transmission is not known. Here we use whole-genome sequencing to investigate the epidemiology of tuberculosis transmission in an unselected population over 6 years. We identified all residents with Oxfordshire postcodes with a Mycobacterium tuberculosis culture or a clinical diagnosis of tuberculosis between Jan 1, 2007, and Dec 31, 2012, using local databases and checking against the national Enhanced Tuberculosis Surveillance database. We used Illumina technology to sequence all available M tuberculosis cultures from identified cases. Sequences were clustered by genetic relatedness and compared retrospectively with contact investigations. The first patient diagnosed in each cluster was defined as the index case, with links to subsequent cases assigned first by use of any epidemiological linkage, then by genetic distance, and then by timing of diagnosis. Although we identified 384 patients with a diagnosis of tuberculosis, country of birth was known for 380 and we sequenced isolates from 247 of 269 cases with culture-confirmed disease. 39 cases were genomically linked within 13 clusters, implying 26 local transmission events. Only 11 of 26 possible transmissions had been previously identified through contact tracing. Of seven genomically confirmed household clusters, five contained additional genomic links to epidemiologically unidentified non-household members. 255 (67%) patients were born in a country with high tuberculosis incidence, conferring a local incidence of 109 cases per 100 000 population per year in Oxfordshire, compared with 3·5 cases per 100 000 per year for those born in low-incidence countries. However, patients born in the low-incidence countries, predominantly UK, were more likely to have pulmonary disease (adjusted odds ratio 1·8 [95% CI 1·2–2·9]; p=0·009), social risk factors (4·4 [2·0–9·4]; p<0·0001), and be part of a local transmission cluster (4·8 [1·6–14·8]; p=0·006). Although inward migration has contributed to the overall tuberculosis incidence, our findings suggest that most patients born in high-incidence countries reactivate latent infection acquired abroad and are not involved in local onward transmission. Systematic screening of new entrants could further improve tuberculosis control, but it is important that health care remains accessible to all individuals, especially high-risk groups, if tuberculosis control is not to be jeopardised.