Lim Leo Kang-Yang, Sng Li Hwei, Win Wah, Chee Cynthia Bin-Eng, Hsu Li Yang, Mak Estelle, Earnest Arul, Ong Marcus Eng-Hock, Cutter Jeffery, Wang Yee Tang
Singapore Tuberculosis Elimination Programme, Tan Tock Seng Hospital, Singapore, Singapore.
Department of Pathology, Singapore General Hospital, Singapore, Singapore.
PLoS One. 2013 Dec 18;8(12):e84487. doi: 10.1371/journal.pone.0084487. eCollection 2013.
Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics.
Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias.
A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates - higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis.
Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally.
结核病在新加坡仍然很常见，自2008年以来发病率一直在上升。我们试图确定本地结核分枝杆菌复合群（MTC）分离株的分子流行病学，识别主要的流行基因型并初步了解传播动态。
对2006年至2012年期间保存在新加坡较大的临床结核病实验室的非重复MTC分离株进行采样，进行间隔寡核苷酸分型（spoligotyping）和多位点可变数目串联重复序列分型（MIRU-VNTR分型），病例数据从新加坡结核病消除计划登记数据库中获取。选择2008年至2012年期间的分离株是因为其具有多重耐药性或潜在的流行病学关联，而早期的分离株是随机选择的。鉴于可能存在的选择偏倚，对早期（2006 - 2007年）和后期（2008 - 2012年）研究阶段分别进行分析。
共对1612株MTC分离株进行了分型，占该时期所有培养阳性结核病病例的13.1% . 91株（5.6%）分离株存在多重耐药性——鉴于选择偏倚，高于全国患病率。大多数分离株属于北京家族（45.8%）和东亚家族（EAI，22.8%）。分别有347例（30.7%）和133例（27.5%）病例通过间隔寡核苷酸分型和MIRU-VNTR分型在早期和后期聚类。这些聚类中的患者往往是华裔、新加坡居民，且分离株属于北京家族。对所有聚类分离株患者的既往接触调查结果进行回顾，未能发现大多数病例的流行病学关联，这表明要么存在未知的传播网络，要么在一个结核病发病率中等的国家中分子分型方法的特异性不足。
我们的研究表明，新加坡MTC菌株分布广泛且具有异质性，根据我们的分子分型结果，过去几年可能存在交叉传播。一个通用的MTC分型计划以及加强接触调查可能有助于进一步了解本地结核病的传播动态。
