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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"email@example.com 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). "
[Show abstract][Hide abstract] ABSTRACT: To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21-0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time.
[Show abstract][Hide abstract] ABSTRACT: In this study we used spoligotyping and 15-loci MIRU-VNTRs for a finer characterization of Mycobacterium tuberculosis strains isolated from patients residing in Guyana (n = 74) and Suriname (n = 80). The mean age of the patients was 38.5 years (36.5 and 40.2 years for Guyana vs. Suriname), with a male-to-female sex-ratio of 3.11 (2.25 and 4.27 for Guyana vs. Suriname). Spoligotyping and 15-loci MIRU-VNTRs led to a total of 41 and 65 different patterns respectively, with an overall clustering rate of 83.8% vs. 68.8%. Combined spoligotyping and VNTR analysis led to the detection of 18 clusters of 2–41 isolates, with an overall clustering of 67.5% and a recent “n − 1” transmission rate of 55.8%. Importantly, Guyana was characterized by a significantly higher percentage of clustered isolates than Suriname (79.7% vs. 56.3%; p = 0.0019). Three big spoligo/MIRU (SIT/MIT) clusters containing >10 isolates each were shared between the 2 countries, and concerned: T1 sublineage cluster 53/861 (n = 41, 37 in Guyana vs. 4 in Suriname); EAI6-BGD1 sublineage cluster 1340/860 (n = 16, 3 in Guyana vs. 13 in Suriname); and T1 sublineage cluster 131/146 (n = 11, 6 in Guyana vs. 5 in Suriname); as well as 2 smaller clusters of 2 and 3 isolates respectively. However, the relative phylogeographical specificities of strains in circulation as well as a lack of drug-resistance observed among strains from Suriname suggested that trans-border transmission of drug-resistant isolates occurred less frequently than thought. Tracing and interrupting transmission channels of a specific clone (SIT53/15-MIT861) should become a priority in Guyana, not only because it is by far most abundant but also because it accounts for almost half of the drug resistant isolates (n = 8/17, 47.1%) in our study, and clustered 5/12 (41.7%) MDR isolates.
"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 . This technique has been used successfully to define chains of ongoing TB transmission, discriminate relapse from re-infection, and to detect laboratory cross-contaminations  . IS6110 is an IS element of 1361 bp flanked by 28 bp inverted repeats which is differently inserted in the genome across strains. "
[Show abstract][Hide abstract] ABSTRACT: The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions. (C) 2014 The Authors. Published by Elsevier Ltd.
Seminars in Immunology 10/2014; 26(6). DOI:10.1016/j.smim.2014.09.012 · 5.17 Impact Factor