The molecular epidemiology of tuberculosis in inner London

Hayward, Andrew; Goss, S.J.; Drobniewski, Francis; Saunders, Nicholas A.; Shaw, Rory; Goyal, Madhu; Swan, A V; Uttley, A.H.C.; Pozniak, Anton; Grace-Parker, J.; Watson, John M.

doi:10.1017/s0950268801006690

Cited by 20 publications

(18 citation statements)

References 24 publications

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“…However, spoligotyping used alone is less discriminatory than RFLP typing and tends to overestimate the number of epidemiological links, so the use of a second method for confirmation of the results is recommended (22). Fingerprinting based on the variable number of tandem DNA repeats (VNTRs) is a further highly reproducible rapid typing method (15) that yields a high level of cluster discrimination comparable to that of RFLP analysis when it is used as a second-line test with spoligotyping (13,26).Use of conventional epidemiological data in combination with these DNA techniques can help answer important questions about the epidemiology of TB in large populations by distinguishing between newly acquired and reactivated disease (1,4,6,7,16,23,32,37). Patients whose isolates have identical…”

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confidence: 99%

“…Use of conventional epidemiological data in combination with these DNA techniques can help answer important questions about the epidemiology of TB in large populations by distinguishing between newly acquired and reactivated disease (1,4,6,7,16,23,32,37). Patients whose isolates have identical patterns (i.e., a cluster) are likely to have been infected recently and can be targeted for epidemiological investigation to identify a chain of transmission, whereas patients whose isolates demonstrate unique patterns are likely to have reactivation of a latent infection.…”

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confidence: 99%

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High Rates of Clustering of Strains Causing Tuberculosis in Harare, Zimbabwe: a Molecular Epidemiological Study

Easterbrook¹,

Gibson

Murad³

et al. 2004

J Clin Microbiol

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We examined the pattern of tuberculosis (TB) transmission (i.e., reactivation versus recent transmission) and the impact of human immunodeficiency virus (HIV) infection in Harare, Zimbabwe. Consecutive adult smear-positive pulmonary TB patients presenting to an urban hospital in Harare were enrolled. A detailed epidemiological questionnaire was completed, and tests for HIV type 1 and CD4 cell counts were performed for each patient. Molecular fingerprinting of the genomic DNA recovered from cultures of sputum was performed by two molecular typing methods: spacer oligonucleotide typing (spoligotyping) and analysis of variable number of tandem DNA repeats (VNTRs). A cluster was defined as isolates from two or more patients that shared the same spoligotype pattern or the same VNTR pattern, or both. DNA suitable for typing was recovered from 224 patients. The prevalence of HIV infection was 79%. Of 187 patient isolates (78.6%) typed by both spoligotyping and analysis of VNTRs, 147 were identified as part of a cluster by both methods. By spoligotyping alone, 84.1% of patient isolates were grouped into 20 clusters. The cluster size was generally <8 patient isolates, although three large clusters comprised 68, 25, and 23 patient isolates. A total of 89.4% of the patient isolates grouped into 12 clusters defined by analysis of VNTRs, with 2 large clusters consisting of 127 and 13 patient isolates, respectively. Thirty-six percent of patient isolates with a shared spoligotype and 17% with a shared VNTR pattern were geographically linked within Harare, but they were not linked on the basis of the patient's home district. In a multivariate analysis, there were no independent predictors of clustering, including HIV infection status. Comparison with the International Spoligotype database (Pasteur Institute, Pointe à Pitre, Guadeloupe) demonstrated that our three largest spoligotype clusters are well recognized and ubiquitous in Africa. In this epidemiologically well characterized urban population with a high prevalence of HIV infection, we identified a very high level of strain clustering, indicating substantial ongoing recent TB transmission. Geographic linkage could be detected in a proportion of these clusters. A small group of actively circulating strains accounted for most of the cases of TB transmission.Tuberculosis (TB) has reemerged as an important public health problem in Zimbabwe. Following a stabilization of the TB rates in the early 1980s at approximately 50 per 100,000 population, since 1987 there has been a dramatic increase to 250 per 100,000 population, which is largely attributable to the human immunodeficiency virus (HIV) epidemic in sub-Saharan Africa (9, 28).Strain-specific markers for the differentiation of Mycobacterium tuberculosis complex strains are reliable tools for the identification of specific strains and are useful for epidemiological studies of TB. The most extensively used differentiation method is restriction fragment length polymorphism (RFLP) typing, which uses the insertion sequence IS6110...

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High Rates of Clustering of Strains Causing Tuberculosis in Harare, Zimbabwe: a Molecular Epidemiological Study

Easterbrook¹,

Gibson

Murad³

et al. 2004

J Clin Microbiol

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“…In countries where the rates of endemic TB are low, the proportion of new cases due to recent infection is estimated to be 38 to 41% in New York, N. Y. (2,22), 40% in San Francisco, Calif. (40), 28% in Berne, Switzerland (25), 46% in Amsterdam, The Netherlands (43), 28% in France (42), 38% in Seville, Spain (38), and 27% in London, England (27).…”

Section: Discussionmentioning

confidence: 99%

“…Outbreaks of drugsensitive and -resistant TB in human immunodeficiency virus (HIV)-positive or -negative individuals have been established in hospitals, schools, bars, prisons, nursing homes, and homeless shelters in the United States, Europe, and elsewhere (8,9,10,13,17,20,21,22,23,29,36,39). These techniques have also been used in population studies to detect outbreaks missed by conventional methods and to estimate transmission levels by comparing the proportion of strains with the same or very similar fingerprint to those of unique isolates (1,2,27,33,40).…”

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Evaluation and Utilization as a Public Health Tool of a National Molecular Epidemiological Tuberculosis Outbreak Database within the United Kingdom from 1997 to 2001

et al. 2003

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The aim of this study was to develop a national model and analyze the value of a molecular epidemiological Mycobacterium tuberculosis DNA fingerprint-outbreak database. Incidents were investigated by the United Kingdom PHLS Mycobacterium Reference Unit (MRU) from June 1997 to December 2001, inclusive. A total of 124 incidents involving 972 tuberculosis cases, including 520 patient cultures from referred incidents and 452 patient cultures related to two population studies, were examined by using restriction fragment length polymorphism IS6110 fingerprinting and rapid epidemiological typing. Investigations were divided into the following three categories, reflecting different operational strategies: retrospective passive analysis, retrospective active analysis, and retrospective prospective analysis. The majority of incidents were in the retrospective passive analysis category, i.e., the individual submitting isolates has a suspicion they may be linked. Outbreaks were examined in schools, hospitals, farms, prisons, and public houses, and laboratory cross-contamination events and unusual clinical presentations were investigated. Retrospective active analysis involved a major outbreak centered on a high school. Contact tracing of a teenager with smear-positive pulmonary tuberculosis matched 14 individuals, including members of his class, and another 60 cases were identified in schools clinically and radiologically and by skin testing. Retrospective prospective analysis involved an outbreak of 94 isoniazid-resistant tuberculosis cases in London, United Kingdom, that began after cases were identified at one hospital in January 2000. Contact tracing and comparison with MRU databases indicated that the earliest matched case had occurred in 1995. Subsequently, the MRU changed to an active prospective analysis targeting linked isoniazid-monoresistant isolates for follow up. The patients were multiethnic, born mainly in the United Kingdom, and included professionals, individuals from the music industry, intravenous drug abusers, and prisoners.

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“…For this purpose, we used a set of low-copy-number isolates from a study of tuberculosis in London during the period from 1995 to 1997 (24). A substantial proportion of the M. tuberculosis isolates in London are from people who have relatively recently arrived from other countries with high rates of tuberculosis or have close connections with such countries (14,24). The high proportion of low-copy-number isolates in London (20%) provides a valuable opportunity for such an analysis.…”

Section: Molecular Typing Ofmentioning

confidence: 99%

Evolutionary Relationships among Strains of Mycobacterium tuberculosis with Few Copies of IS 6110

et al. 2003

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Molecular typing ofMycobacterium tuberculosis by using IS6110 shows low discrimination when there are fewer than five copies of the insertion sequence. Using a collection of such isolates from a study of the epidemiology of tuberculosis in London, we have shown a substantial degree of congruence between IS6110 patterns and both spoligotype and PGRS type. This indicates that the IS6110 types mainly represent distinct families of strains rather than arising through the convergent insertion of IS6110 into favored positions. This is supported by identification of the genomic sites of the insertion of IS6110 in these strains. The combined data enable identification of the putative evolutionary relationships of these strains, comprising three lineages broadly associated with patients born in South Asia (India and Pakistan), Africa, and Europe, respectively. These lineages appear to be quite distinct from M. tuberculosis isolates with multiple copies of IS6110.The international standard method for typing Mycobacterium tuberculosis depends on the polymorphism detected with the insertion sequence IS6110 (17,41,47). In most populations, multicopy strains (with five or more copies of IS6110) form a substantial majority of isolates of M. tuberculosis (24,33,40,42). Isolates with only a few copies of IS6110 show much less polymorphism, necessitating the use of additional typing methods such as spoligotyping (20) or PGRS typing (7). The implied assumption behind the use of secondary typing to define clusters of low-copy-number isolates is that the combined rate of variation for the low-copy-number isolates (the product of the two molecular clocks) is equivalent to the single rate of variation of the IS6110 pattern in the multiple-copynumber strains.The reduced polymorphism of IS6110 in low-copy-number strains is assumed to reflect the occupation of a limited number of chromosomal sites by the insertion sequence in such strains. One hypothesis is that this is due to frequent independent transposition into the same chromosomal sites (which would be true hot spots). An alternative hypothesis is that the low degree of polymorphism arises from a lack of mobility of IS6110 in such strains (i.e., the IS6110 molecular clock operates more slowly) (5, 43). The first hypothesis would lead to the prediction that additional independent typing methods would yield widely dispersed results. However, if the second hypothesis were true, independent typing methods would be predicted to show substantial congruence.In addition, the assumption that a limited number of chromosomal sites are occupied in low-copy-number strains needs to be tested. Several studies have shown that the overall distribution of IS6110 inserts is nonrandom, either by determining band sizes (13,25) or by examining the occurrence of inserts in specific regions of the genome (IS6110 preferential loci) (8-10, 44). Microarrays have also been used (22) to locate the insertions of IS6110 to such regions or to specific genes. For studies of evolutionary relationships, it is necess...

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The molecular epidemiology of tuberculosis in inner London

Cited by 20 publications

References 24 publications

High Rates of Clustering of Strains Causing Tuberculosis in Harare, Zimbabwe: a Molecular Epidemiological Study

High Rates of Clustering of Strains Causing Tuberculosis in Harare, Zimbabwe: a Molecular Epidemiological Study

Evaluation and Utilization as a Public Health Tool of a National Molecular Epidemiological Tuberculosis Outbreak Database within the United Kingdom from 1997 to 2001

Evolutionary Relationships among Strains of Mycobacterium tuberculosis with Few Copies of IS 6110

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