Couvin David, Rastogi Nalin
WHO Supranational Tuberculosis Reference Laboratory, Tuberculosis and Mycobacteria Unit, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
WHO Supranational Tuberculosis Reference Laboratory, Tuberculosis and Mycobacteria Unit, Institut Pasteur de la Guadeloupe, Abymes, Guadeloupe, France.
Tuberculosis (Edinb). 2015 Jun;95 Suppl 1:S177-89. doi: 10.1016/j.tube.2015.02.023. Epub 2015 Feb 13.
We argue in favor of a concerted and coordinated response to stop tuberculosis (TB) by monitoring global TB spread, drug-resistance surveillance and populations at risk using available molecular and web tools to identify circulating clones of Mycobacterium tuberculosis complex (MTBC). We took specific example of the Beijing lineage associated with worldwide emergence of both multiple, and extensively drug resistant (MDR/XDR)-TB. The study dataset (n=10,850 isolates, 92 countries of patient origin) was extracted from our multimarker SITVIT2 database on MTBC genotyping (n=111,635 isolates, 169 countries of patient origin). Epidemiological and demographic information in conjunction with spoligotyping (n=10,850), MIRU-VNTR minisatellites (n=2896), and drug resistance (n=2846) data was mapped at macro-geographical (United Nations subregions) and country level, followed by statistical, bioinformatical, and phylogenetical analysis. The global male/female sex ratio was 1.96, the highest being 4.93 in Russia vs. range of 0.8-1.13 observed in Central America, Caribbean, Eastern Africa and Northern Europe (p < 0.0001). The major patient age-group was 21-40 yrs worldwide except Japan (with majority of patients >60 yrs). Younger patients were more common in South America, South Asia, and Western Africa since 25-33% of TB cases due to Beijing genotype occurred in the age group 0-20 yrs. A continuous progression in the proportion of MDR and XDR strains is visible worldwide since 2003 and 2009 respectively. Pansusceptible TB mainly concerned older patients >60 yrs (44%) whereas Drug resistant, MDR and XDR-TB concerned patients preferentially aged 21-40 yrs (between 52 and 58%). Although the proportion of SIT1 pattern vs. other patterns was very high (93%); the proportion of MDR was highest for an emerging genotype SIT190 (p < 0.0001). Lastly, proportion of pansusceptible strains was highest in Japan, while MDR/XDR strains were most common in Russia and Northern Europe. We underline remarkable macro/micro-geographical cleavages in phylogenetic and epidemiologic diversity of Beijing genotype, with phylogeographical specificity of certain genotypes.
我们主张通过利用现有的分子和网络工具监测全球结核病传播、耐药性监测以及高危人群，以识别结核分枝杆菌复合群（MTBC）的流行克隆，从而采取协调一致的应对措施来遏制结核病（TB）。我们以与全球多重耐药和广泛耐药结核病（MDR/XDR-TB）出现相关的北京家族为例。研究数据集（n = 10,850株分离株，来自92个国家的患者）取自我们关于MTBC基因分型的多标记SITVIT2数据库（n = 111,635株分离株，来自169个国家的患者）。将流行病学和人口统计学信息与 spoligotyping（n = 10,850）、MIRU-VNTR微卫星（n = 2896）以及耐药性（n = 2846）数据在宏观地理层面（联合国次区域）和国家层面进行映射，随后进行统计、生物信息学和系统发育分析。全球男女比例为1.96，俄罗斯最高，为4.93，而在中美洲、加勒比地区、东非和北欧观察到的比例范围为0.8 - 1.13（p < 0.0001）。除日本外（大多数患者年龄>60岁），全球主要患者年龄组为21 - 40岁。在南美洲、南亚和西非，年轻患者更为常见，因为0 - 20岁年龄组中25 - 33%的结核病病例归因于北京基因型。自2003年和2009年以来，全球耐多药和广泛耐药菌株的比例分别呈持续上升趋势。对药物敏感的结核病主要涉及年龄>60岁的老年患者（44%），而耐药、耐多药和广泛耐药结核病则主要涉及年龄在21 - 40岁的患者（52%至58%）。尽管SIT1型与其他类型的比例非常高（93%）；但新兴基因型SIT190的耐多药比例最高（p < 0.0001）。最后，对药物敏感菌株的比例在日本最高，而耐多药/广泛耐药菌株在俄罗斯和北欧最为常见。我们强调北京基因型在系统发育和流行病学多样性方面存在显著的宏观/微观地理差异，以及某些基因型的系统地理特异性。
