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基于基因分型聚类的方法定量分析 7 年间瓜德罗普岛的近期结核传播:危险因素分析及卫生保健可及性研究。

Use of genotyping based clustering to quantify recent tuberculosis transmission in Guadeloupe during a seven years period: analysis of risk factors and access to health care.

出版信息

BMC Infect Dis. 2013 Aug 2;13:364. doi: 10.1186/1471-2334-13-364.

Abstract

BACKGROUND

The present study aimed to characterize Mycobacterium tuberculosis population structure and to identify transmission chains and risk factors by prospective molecular typing in conjunction with conventional epidemiological investigations in the French overseas department of Guadeloupe.

METHODS

The study included all the culture-positive TB cases (1 clinical isolate per patient; n = 129) diagnosed between a seven year period (April 4th, 1999 to December 31st, 2005). Prospective molecular typing was performed using spoligotyping and VNTRs, and a subset of 44 M. tuberculosis isolates found to be clustered was retrospectively typed using 12-loci MIRUs. Data were compared using the SITVIT2 database, followed by analysis of risk factors in function of clustering of the isolates and available demographic and socioeconomic data.

RESULTS

The study sample was characterized by a majority of new cases (87.4%); a moderate proportion of drug-resistance (7.8%); a high level of immigration (51.2% foreign-born) originating from high TB/HIV incidence neighboring islands such as Haiti or Dominican Republic; lower socioeconomic conditions (70.7% of jobless, average income 824 EUR/month); and a significantly higher proportion of TB/HIV co-infected cases (38.2% vs. 8.5%; p < 0.001), and extrapulmonary disease (18.2% vs. 4.8%; p < 0.02) among migrants as compared to French patients. The study revealed an important delay in access to healthcare with a median delay of 74.5 days between the 1st symptoms and clinical suspicion of TB. Prospective molecular typing based on spoligotyping and 5-loci VNTRs showed that evolutionary recent Euro-American lineages predominated in Guadeloupe (91.5% of isolates). In conjunction with epidemiological data, it allowed to estimate a recent transmission rate of 18.6%, which was close to the rate of 16.7% estimated using retrospective 12-loci MIRU typing. Although a higher proportion of cases in older age-group were apparently linked to reactivation; univariate analysis of risk factors did not allow pinpointing specific risk factors for a patient to belong to a TB transmission group.

CONCLUSIONS

Ongoing TB transmission in the insular, low TB-incidence setting of Guadeloupe can be defined as follows: (i) a significant proportion of imported cases of the disease from neighboring islands; (ii) significantly higher TB/HIV coinfection among foreign-born cases; and, (iii) a higher proportion of cases affecting older age-group among French patients due to reactivation. This study emphasizes the need for universal typing using spoligotyping and 15-loci MIRUs in prospective studies.

摘要

背景

本研究旨在通过前瞻性分子分型与传统流行病学调查相结合,对法属海外省瓜德罗普的结核分枝杆菌种群结构进行特征描述,并确定传播链和危险因素。

方法

本研究纳入了在 7 年期间(1999 年 4 月 4 日至 2005 年 12 月 31 日)诊断的所有培养阳性的结核病例(每位患者 1 例临床分离株;n=129)。采用 spoligotyping 和 VNTRs 进行前瞻性分子分型,并对聚类发现的 44 株结核分枝杆菌分离株进行回顾性 12 位基因 MIRU 分型。使用 SITVIT2 数据库比较数据,然后根据分离株聚类和可用的人口统计学和社会经济学数据分析危险因素。

结果

研究样本的特征是新发病例(87.4%)占比较大;耐药比例(7.8%)中等;移民比例高(51.2%为外国出生),原籍为海地或多米尼加共和国等高结核/艾滋病毒发病率的邻近岛屿;社会经济条件较差(70.7%无工作,平均月收入 824 欧元);与法国患者相比,结核/艾滋病毒合并感染病例(38.2%比 8.5%;p<0.001)和肺外疾病(18.2%比 4.8%;p<0.02)的比例明显更高。研究显示,移民患者获得医疗保健的时间明显延迟,从出现症状到临床怀疑结核病的中位时间为 74.5 天。基于 spoligotyping 和 5 位 VNTRs 的前瞻性分子分型显示,最近的欧裔美洲谱系在瓜德罗普占主导地位(91.5%的分离株)。结合流行病学数据,估计最近的传播率为 18.6%,这与使用回顾性 12 位基因 MIRU 分型估计的 16.7%传播率接近。尽管年龄较大的病例比例较高似乎与再激活有关;但危险因素的单因素分析无法确定患者属于结核传播组的特定危险因素。

结论

在瓜德罗普岛这种岛屿性、低结核发病率的环境中,持续存在结核传播,具体特征如下:(i)从邻近岛屿输入的疾病输入病例占比高;(ii)外国出生病例中结核/艾滋病毒合并感染率显著较高;以及,(iii)由于再激活,法国患者中年龄较大的病例比例较高。本研究强调在前瞻性研究中使用 spoligotyping 和 15 位基因 MIRU 进行通用分型的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e33/3750484/74b56610e348/1471-2334-13-364-1.jpg

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