The Epidemiology of Tuberculosis in San Francisco -- A Population-Based Study Using Conventional and Molecular Methods

Department of Medicine, Stanford Medical School, Calif. 94305.
New England Journal of Medicine (Impact Factor: 55.87). 07/1994; 330(24):1703-9. DOI: 10.1056/NEJM199406163302402
Source: PubMed


The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted.
We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed.
Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease.
Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

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Available from: Julie Parsonnet, Nov 04, 2014
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    • " Since the 1990s, methods such as RFLP based on the insertion element IS6110 (van Embden et al., 1993) have been used to distinguish clusters of patients with shared DNA-fingerprint patterns, suggesting recent transmission (Small et al., 1994), but within the clusters, these methods cannot distinguish who transmitted to whom. Whole genome sequencing provides far greater resolution, and if data are collected in a whole population over several years, single nucleotide polymorphisms (SNPs) can be used to construct transmission networks (Bryant et al., 2013; Walker et al., 2013, 2014). "
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    • "cluster 1340/860 designates all strains sharing SIT1340 and 15-MIT860. The recent transmission rate was calculated using the n À 1 method (Small et al., 1994). "
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    • "Restriction fragment length polymorphisms (RFLP) typing is based on differences in copy number and the differential genomic location of the insertion sequence (IS) 6110, and became the first gold standard method for genotyping MTBC [15]. This technique has been used successfully to define chains of ongoing TB transmission, discriminate relapse from re-infection, and to detect laboratory cross-contaminations [16] [17]. IS6110 is an IS element of 1361 bp flanked by 28 bp inverted repeats which is differently inserted in the genome across strains. "
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