Chapter 3 : Molecular Epidemiology of

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Molecular Epidemiology of , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap03-1.gif /docserver/preview/fulltext/10.1128/9781555817657/9781555812959_Chap03-2.gif


Epidemiologic investigations were limited because there are relatively few phage types, the most common of which are shared by many isolates, and antibiograms are useful only for drug-resistant strains. The modern genotyping methods and the relevance of these methods to the control and understanding of the pathogenesis of tuberculosis (TB) have recently been reviewed. Southern blots of DNA electrophoresed on agarose gels and probed with a fragment of IS that lies upstream of the single PvuII site provide restriction fragment length polymorphism (RFLP) patterns. Polymorphisms in the direct-repeat (DR) locus tend to group strains into larger groups than does Insertion sequence (IS) analysis and have been used to link strains to specific geographic areas. Polymorphisms in tandemly repeated minisatellite loci caused by unequal crossing over are the basis for human forensic DNA typing. Recently, several groups have used synonymous single-nucleotide polymorphisms (SNPs) as a tool to type strains. Point mutations are categorized as either nonsynonymous or synonymous, depending on whether the substitution leads to a change in amino acid sequence and thus in the protein for which the sequence codes. Genotyping of suspected false-positive cultures plays an important role in confirming false-positive cases and possible sources of cross-contamination. In a recent investigation in the United States, DNA fingerprinting was used to evaluate epidemiologically linked pairs found during contact investigations. The fact that strain W was originally associated with an outbreak of multidrug-resistant TB (MDRTB) confounds the issue of transmissibility/virulence and drug resistance.

Citation: Cave M, Murray M, Nardell E. 2005. Molecular Epidemiology of , p 33-46. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch3
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Chromosome of hypothetical strain X and genotyping of BCG, the laboratory strain H37Rv, and strain X on the basis of ISinsertion sites and MIRUs. The top right-hand panel shows the chromosome of hypothetical strain X. sites are indicated by the arrows. The top left-hand panel shows the results of IS-based genotyping. Mycobacterial DNA is digested with the restriction enzyme . The ISprobe hybridizes to ISDNA to the right of the site in IS. The size of each hybridizing fragment depends on the distance from this site to the next site in the adjacent DNA (fragments a through f), as reflected by gel electrophoresis of the DNA fragments of BCG, H37Rv, and X. The horizontal lines to the right of the electrophoretic strip indicate the extent of the distribution of fragments in the gel, including fragments that contain no IS. The three bottom panels show the results of MIRU-based genotyping. MIRUs contain repeat units, and MIRU analysis involves the use of PCR amplification and gel electrophoresis to categorize the number and size of the repeats at 12 independent loci, each of which has a unique repeated sequence. The sizes of molecular weight markers (lanes M) and PCR products for loci A, B, C, and D (lanes A to D, respectively), in BCG, H37Rv, and X are shown. The specific sizes of the various MIRUs in each strain result in a distinctive fingerprint for the strain. (Modified from reference 4 with permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved.)

Citation: Cave M, Murray M, Nardell E. 2005. Molecular Epidemiology of , p 33-46. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Spoligotyping. The DR locus is a chromosomal region that contains 10 to 50 copies of a 36-bp direct repeat, separated by spacer DNA with various sequences, each of which is 37 to 41 bp. A copy of ISis inserted within a 36-bp DR in the middle of the DR locus in most strains. strains have the same overall arrangement of spacers but differ in terms of the presence or absence of specific spacers. Spoligotyping involves PCR amplification of the DR locus, followed by hybridization of the labeled PCR products to a membrane that contains covalently bound oligonucleotides corresponding to each of 43 spacers. Individual strains have positive or negative signals for each spacer. The top section shows the 43 DR (rectangles) and spacers (horizontal lines) used in spoligotyping. The middle section shows the products of PCR amplification of spacers 1 through 6 in BCG, strain H37Rv, and hypothetical strain X, with the use of primers (white and black arrows) at each end of the DR loci. The bottom section shows the spoligotypes of the three strains. (Reprinted from reference 4 with permission. Copyright © 2003 Massachusetts Medical Society. All rights reserved.)

Citation: Cave M, Murray M, Nardell E. 2005. Molecular Epidemiology of , p 33-46. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Alland, D.,, T. S. Whittam,, M. B. Murray,, M. D. Cave,, M. H. Hazbon,, K. Dix,, M. Kokoris,, A. Duesterhoeft,, J. A Eisen,, C. M. Fraser,, and R. D. Fleischmann. 2003. Modeling bacterial evolution with comparative-genome-based marker systems: application to Mycobacterium tuberculosis evolution and pathogenesis. J. Bacteriol. 185: 3392 3399.
2. Anh, D. D.,, M. W. Borgdorff,, L. N. Van,, N. T. Lan,, T. van Gorkom,, and K. Kremer. 2000. Mycobacterium tuberculosis Beijing genotype emerging in Vietnam. Emerg. Infect. Dis. 6: 302 305.
3. Bandera, A.,, A. Gori,, L. Catozzi,, A. Degli Esposti,, G. Marchetti,, C. Molteni,, G. Ferrario,, L. Codecasa,, V. Penati,, A. Matteelli,, and F. Franzetti. 2000. Molecular epidemiology study of exogenous reinfection in an area with a low incidence of tuberculosis. J. Clin. Microbiol. 39: 2213 2218.
4. Barnes, P. F.,, and M. D. Cave. 2003. Molecular epidemiology of tuberculosis. N. Engl. J. Med. 349: 1149 1156.
5. Beggs, M. L.,, K. D. Eisenach,, and M. D. Cave. 2000. Mapping of IS 6110 insertion sites in two epidemic strains of Mycobacterium tuberculosis. J. Clin Microbiol. 38: 2923 2928.
6. Bennett, D. E.,, I. M. Onorato,, B. A. Ellis,, J. T. Crawford,, B. Schable,, R. Byers,, J. S. Kammerer,, and C. R Braden. 2002. DNA fingerprinting of Mycobacterium tuberculosis isolates from epidemiologically linked case pairs. Emerg. Infect. Dis. 8: 1224 1229.
7. Bifani, P. J.,, B. Mathema,, N. E. Kurepina,, B. N. Kreiswirth. 2002. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol. 10: 45 52.
8. Bifani, P. J.,, B. Mathema,, Z. Liu,, S. L. Moghazeh,, B. Shopsin,, B. Tempalski,, R. Driscol Frothingham,, J. M. Musser,, P. Alcabes,, and B. N. Kreiswirth. 1999. Identification of a W variant outbreak of Mycobacterium tuberculosis via population- based molecular epidemiology. JAMA 282: 2321 2327.
9. Bishai, W. R.,, A. M. Dannenberg, Jr.,, N. Parrish,, R. Ruiz,, P. Chen,, B. C. Zook,, W. Johnson,, J. W Boles,, and M. L Pitt. 1999. Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in rabbits evaluated by Lurie’s pulmonary tubercle count method. Infect. Immun. 67: 4931 4934.
10. Borgdorff, M. W.,, N. Nagelkerke,, D. van Soolingen,, P. E. de Haas,, J. Veen,, and J. D. van Embden. 1998. Analysis of tuberculosis transmission between nationalities in the Netherlands in the period 1993-1995 using DNA fingerprinting. Am. J. Epidemiol. 147: 187 195.
11. Braden, C. R.,, G. P. Morlock,, C. L. Woodley,, K. M. Johnson,, A. C. Colombel,, M. D. Cave,, Z. Yang,, S. E Valway,, I. M. Onorato,, and J. T Crawford. 2001. Simultaneous infection with multiple strains of M. tuberculosis. Clin. Infect. Dis. 33: e42 e47.
12. Burman, W. J.,, and R. Reves. 2000. Review of false-positive cultures for Mycobacterium tuberculosis and recommendations for avoiding unnecessary treatment. Clin. Infect Dis. 31: 1390 1395.
13. Butler, W. R.,, W. H. Hass,, and J. T. Crawford. 1996. Automated DNA fingerprinting analysis of Mycobacterium tuberculosis using fluorescent detection of PCR products. J. Clin. Microbiol. 34: 1801 1803.
14. Caminero, J. A.,, M. J. Pena,, M. I. Campos-Herrero,, J. C. Rodriguez,, O. Afonso,, C. Martin,, J. M. Pavon,, M. J. Torres,, M. Burgos,, P. Cabrera,, P. M. Small,, and D. A Enarson. 2001. Exogenous reinfection with tuberculosis on a European island with moderate incidence of disease. Am. J. Respir. Crit. Care. Med. 163: 717 720.
15. Cave, M. D.,, K. D. Eisenach,, P. F. McDermott,, J. J. Bates,, and J. T. Crawford. 1991. IS 6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting. Mol. Cell. Probes 5: 73 80.
16. Cave, M. D.,, K. D. Eisenach,, G. Templeton,, M. Salfinger,, G. Mazurek,, J. Bates,, and J. T. Crawford. 1994. Stability of DNA fingerprint pattern produced with IS 6110 strains of Mycobacterium tuberculosis. J. Clin. Microbiol. 32: 262 266.
17. Classen, C.N.,, R. Warren,, M. Richardson,, J. H. Hauman,, R. P. Gie,, J. H. Ellis,, P. D. van Helden,, and N. Beyers. 1999. Impact of social interactions in the community on the transmission of tuberculosis in a high incidence area. Thorax 54: 136 140.
18. Cole, S. T.,, R. Brosch,, J. Parkhill,, T. Garnier,, C. Churcher,, D. Harris,, S. V. Gordon,, L. Eiglmeier,, S. Gas,, C. E. Barry, III, F. Tekaia, K. Badcock, D. Basham, D. Brown, T. Chillingworth, R. Connor, R. Davies, K. Devlin, T. Feltwell, S. Gentles, N. Hamlin, S. Holroyd, T. Hornsby, K. Jagels, J. Krogh, J. Mclean, S. Moule, L. Murphy, K. Oliver, J. Osborne, M. A. Quail, M. A. Rajandream, J. Rogers, S. Rutter, K. Seeger, J. Skelton, R. Squares, S. Squares, J. E. Sulston, K. Taylor, S. Whitehead, and B. G. Barrell. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537 544.
19. Crawford, J. T.,, C. R. Braden,, B. A. Schable,, and I. M. Onorato. 2002. National Tuberculosis Genotyping and Surveillance Network: design and methods. Emerg. Infect. Dis. 8: 1192 1196.
20. Cronin, W. A.,, J. E. Golub,, M. J. Lathan,, L. N. Mukasa,, N. Hooper,, J. H. Razaq,, N. G. Baruch,, D. Mulcahy,, W. H. Benjamin,, L. S. Magder,, G. T. Strickland,, and W. R. Bishai. 2002. Molecular epidemiology of tuberculosis in a low-to moderate-incidence state: are contact investigations enough? Emerg. Infect. Dis. 8: 1271 1279.
21. Dale, J. W.,, D. Brittain,, A. A. Cataldi,, D. Cousins,, J. T. Crawford,, J. Driscoll,, H. Heersma,, T. Lilleback,, T. Quitugua,, N. Rastogi,, R. A Skuce,, C. Sola,, D. van Soolingen,, and V. Vincent. 2001. Spacer oligonucleotide typing of bacteria of the Mycobacterium tuberculosis complex: recommendations for standardized nomenclature. Int. J. Tuberc. Lung Dis. 5: 216 219.
22. Daley, C. L.,, P. M. Small,, G. F. Schecter,, G. K. Schoolnik,, R. A. McAdam,, and W. R. Jacobs, Jr. 1992. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N. Engl. J. Med. 326: 231 235.
23. Dillaha, J. A.,, Z. Yang,, K. Ijaz,, K. D. Eisenach,, M. D. Cave,, F. J. Wilson,, W. W. Stead,, and J. H. Bates. 2002. Transmission of Mycobacterium tuberculosis in a rural community, Arkansas, 1945-2000. Emerg. Infect. Dis. 8: 1246 1248.
24. Dobbs, K. G.,, K. H. Lok,, F. Bruce,, D. Mulcahy,, W. H. Benjamin,, and N. E. Dunlap. 2001. Value of Mycobacterium tuberculosis fingerprinting as a tool in a rural state surveillance program. Chest 120: 1877 1882.
25. Doroudchi, M.,, K. Kremer,, E. A. Basiri,, M. R. Kadivar,, D. van Soolingen,, and A. A. Ghaderi. 2000. IS 6110-RFLP and spoligotyping of Mycobacterium tuberculosis isolates in Iran. Scand. J. Infect. Dis. 32: 663 668.
26. Fandinho, F. C.,, A. L. Kritski,, C. Hofer,, H. Conde, Jr.,, R. M. Ferreira,, M. H. Saad,, M. G. Silva,, L. W. Riley,, and L. S. Fonseca. 2000. RFLP patterns and risk factors for recent tuberculosis transmission among hospitalized tuberculosis patients in Rio de Janeiro, Brazil. Trans. R. Soc. Trop. Med. Hyg. 94: 271 275.
27. Fang, Z.,, and K. J. Forbes. 1997. A Mycobacterium tuberculosis IS 6110 preferential locus ( ipl) for insertion into the genome. J. Clin. Microbiol. 35: 479 481.
28. Fleischmann, R. D.,, D. Alland,, J. A. Eisen,, L. Carpenter,, O. White,, J. Peterson,, R. DeBoy,, R. Dodson,, M. Gwinn,, D. Haft,, E. Hickey,, J. F. Kolonay,, W. C. Nelson,, L. A. Umayam,, M. Ermolaeva,, S. L. Salzberg,, A. Delcher,, T. Utterback,, J. Weidman,, H. Khouri,, J. Gill,, A. Mikula,, W. Bishai,, W. R. Jacobs, Jr.,, J. C. Venter,, and C. M. Fraser. 2002. Wholegenome comparison of Mycobacterium tuberculosis clinical and laboratory strains. J. Bacteriol. 184: 5479 5490.
29. Fomukong, N.,, M. Beggs,, H. el Hajj,, G. Templeton,, K. Eisenach,, and M. D. Cave. 1998. Differences in the prevalence of IS 6110 insertion sites in Mycobacterium tuberculosis strains: low and high copy number of IS 6110. Tubercle. Lung Dis. 78: 109 116
30. Fraser, C. M.,, J. Eisen,, R. D. Fleischmann,, K. A. Ketchum,, and S. Peterson. 2000. Comparative genomics and understanding of microbial biology. Emerg. Infect. Dis. 6: 505 512.
31. Frieden, T. R.,, C. L. Woodley,, J. T. Crawford,, D. Lew,, and S. M. Dooley. 1996. The molecular epidemiology of tuberculosis in New York City: the importance of nosocomial transmission and laboratory error. Tubercle. Lung Dis. 77: 407 413.
32. Friedman, C. R.,, M. Y. Stoeckle,, B. N. Kreiswirth,, W. D. Johnson, Jr.,, S. M. Manoach,, J. Berger,, K. Sathianathan, A. Hafner,, and L. W. Riley. 1995. Transmission of multidrugresistant tuberculosis in a large urban setting. Am. J. Respir. Crit. Care Med. 152: 3
33. Frothingham, R.,, and W. A. Meeker-O’Connell. 1998. Genetic diversity in the Mycobacterium tuberculosis complex based on variable numbers of tandem DNA repeats. Microbiology 144: 1189 1196.
34. Garcia-Garcia, M. L.,, A. Ponce de Leon,, M. E. Jimenez- Corona,, A. Jimenez-Corona,, M. Palacios-Martinez,, S. Balandrano- Campos,, L. Ferreyra-Reyes,, L. Juarez-Sandino,, J. Sifuentes-Osornio,, H. Olivera-Diaz,, J. L. Valdespino-Gomez,, and P. M. Small. 2000. Clinical consequences and transmissibility of drug-resistant tuberculosis in southern Mexico. Arch. Intern. Med. 13: 630 636.
35. Githui, W. A.,, M. P. Hawken,, E. S. Juma,, P. Godfrey-Faussett,, O. B. Swai,, D. K. Kibuga,, J. D. Porter,, S. M. Wilson,, and F. A. Drobniewski. 2000. Surveillance of drug-resistant tuberculosis and molecular evaluation of transmission of resistant strains in refugee and non-refugee populations in North-Eastern Kenya. Int. J. Tuberc. Lung Dis. 4: 947 955.
36. Glynn, J. R.,, E. Vynnycky,, and P. E. Fine. 1999. Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques. Am. J. Epidemiol. 149: 366 371.
37. Godfrey-Faussett, P.,, P. R. Mortimer,, P. A. Jenkins,, and N. G. Stoker. 1992. Evidence of transmission of tuberculosis by DNA fingerprinting. Br. Med. J. 305: 221 223.
38. Golub, J. E.,, W. A. Cronin,, O. O. Obasanjo,, W. Coggin,, K. Moore,, D. S. Pope,, D. Thompson,, T. R. Sterling,, S. Harrington,, W. R. Bishai,, and R. E. Chaisson. 2001. Transmission of Mycobacterium tuberculosis through casual contact with an infectious case. Arch. Intern. Med. 161: 2254 2258.
39. Haas, W. H.,, W. R. Butler,, C. L. Woodley,, and J. T. Crawford. 1993. Mixed-linker polymerase chain reaction: a new method for rapid fingerprinting of isolates of the Mycobacterium tuberculosis complex. J. Clin. Microbiol. 31: 1293 1298.
40. Hermans, P. W. M.,, D. van Soolingen,, E. M. Bik,, P. E. W. de Haas,, J. W. Dale,, and J. D. A. van Embden. 1991. The insertion element IS 987 for Mycobacterium bovis BCG is located in a hot spot integration region for insertion elements in M. tuberculosis strains. Infect. Immun. 59: 2695 2705.
41. Horn, D. L.,, D. Hewlett, Jr.,, W. H. Haas,, W. R. Butler,, C. Alfalla,, E. Tan,, A. Levine,, A. Nayak,, and S. M. Opal. 1994. Superinfection with rifampin-isoniazid-streptomycinethambutol (RISE)-resistant tuberculosis in three patients with AIDS: confirmation by polymerase chain reaction fingerprinting. Ann. Intern. Med. 121: 115 116.
42. Jasmer, R. M.,, M. Roemer,, J. Hamilton,, J. Bunter,, C. R. Braden,, T. M. Shinnick,, and E. P. Desmond. 2002. A prospective, multicenter study of laboratory cross-contamination of Mycobacterium tuberculosis cultures. Emerg. Infect. Dis. 8: 1260 1263.
43. Kamerbeek, J.,, L. Schouls,, A. Kolk,, M. van Agtervveld,, D. van Soolingen,, S. Kuijper,, A. Bunschoten,, H. Molhuizen,, R. Shaw,, M. Goyal,, and J. D. A. van Embden. 1997. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J. Clin. Microbiol. 35: 907 914.
44. Kato-Maeda, M.,, J. T. Rhee,, T. R. Gingeras,, H. Salamon,, J. Drenkow,, N. Smittipat,, and P. M. Small. 2001. Comparing genomes within the species Mycobacterium tuberculosis. Genome Res. 11: 547 554.
45. Kelley, C. L.,, and F. M. Collins. 1999. Growth of a highly virulent strain of Mycobacterium tuberculosis in mice of differing susceptibility to tuberculous challenge. Tubercle Lung Dis. 79: 367 70.
46. Kline, S. E.,, L. L. Hedemark,, and S. F. Davies. 1995. Outbreak of tuberculosis among regular patrons of a neighborhood bar. N. Engl. J. Med. 333: 222 227.
47. Kong, P. M.,, J. Tapy,, P. Calixto,, W. J. Burman,, R. R. Reves,, Z. Yang,, and M. D. Cave. 2002. Skin-test screening and tuberculosis transmission among the homeless. Emerg. Infect. Dis. 8: 1280 1284.
48. Lok, K.,, W. Benjamin,, M. E. Kimerling,, V. Pruitt,, M. Lathan,, J. Raquez,, N. Hooper,, W. Cronin,, and N. Dunlap. 2002. Molecular differentiation of Mycobacterium tuberculosis strains without IS 6110 insertions. Emerg. Infect. Dis. 8: 1310 1313.
49. Manca, C.,, L. Tsenova,, C. E. Barry, III, A. Bergtold, S. Freeman, P. A. Haslett, J. M. Musser, V. H. Freedman, and G. Kaplan. 1999. Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates. J. Immun. 162: 6740 6746.
50. March, F.,, P. Coll,, R. A. Guerrero,, E. Busquets,, J. A. Cayla,, and G. Prats. 2000. Predictors of tuberculosis transmission in prisons: an analysis using conventional and molecular methods. AIDS 14: 525 535.
51. Mazars, E.,, S. Lesjean,, A.-L. Banuls,, M. Gilbert,, V. Vincent,, B. Gicquel,, M. Tibayrenc,, C. Locht,, and P. Supply. 2001. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology. Proc. Natl. Acad. Sci. USA 98: 1901 1906.
52. Mazurek, C. H.,, M. D. Cave,, K. D. Eisenach,, R. J. Wallace,, J. H. Bates,, and J. T. Crawford. 1991. Chromosomal DNA fingerprint patterns produced with IS 6110 as a strain specific marker for the epidemiologic study of tuberculosis. J. Clin. Microbiol. 29: 2030 2033.
53. McNabb, S. J.,, C. R. Braden,, and T. R. Navin. 2002. DNA fingerprinting of Mycobacterium tuberculosis: lessons learned and implications for the future. Emerg. Infect. Dis. 1314 1319.
54. Middlebrook, G.,, and M. L. Cohn. 1953. Some observations on the pathogenicity of isoniazid-resistant variants of the tubercle bacilli. Science 118: 297 299.
55. Miller, A.C.,, W. R. Butler,, and B. McInnis. 2002. Clonal relationships in a shelter-associated outbreak of drug-resistant tuberculosis: 1983-1997. Int. J. Tuberc. Lung Dis. 6: 872 878.
56. Miller, A. C.,, S. Sharnprapai,, R. Suruki,, E. Corkren,, E. A. Nardell,, J. R. Driscoll,, M. McGarry,, H. Taber,, and S. Etkind. 2002. Impact of genotyping of Mycobacterium tuberculosis on public health practice in Massachusetts. Emerg. Infect. Dis. 8: 1285 1292.
57. Murray, M. 2002. Sampling bias in the molecular epidemiology of tuberculosis. Emerg. Infect. Dis. 8: 363 369.
58. Murray, M. B.,, and D. A. Alland. 2002. Methodological problems in the molecular epidemiology of tuberculosis. Am. J. Epidemiol. 155: 565 571.
59. Nardell, E.,, B. McInnis,, B. Thomas,, and S. Weidhaas. 1986. Exogenous reinfection with tuberculosis in a shelter for the homeless. N. Engl. J. Med. 315: 1570 1574.
60. Northrup, J. M.,, A. C. Miller,, E. Nardell,, S. Sharnprapai,, S. Etkind,, J. Driscoll,, M. McGarry,, H. W. Taber,, P. Elvin,, N. L. Qualls,, and C. R. Braden. 2002. Estimated costs of false laboratory diagnoses of tuberculosis in three patients. Emerg. Infect. Dis. 8: 1264 1270.
61. Pfyffer, G. E.,, A. Strassle,, N. Rose,, R. Wirth,, O. Brandli,, and H. Shang. 1998. Transmission of tuberculosis in the metropolitan area of Zurich: a 3 year survey based on DNA fingerprinting. Eur. Respir. J. 11: 804 808.
62. Pineda-Garcia, L.,, A. Ferrera,, and S. E. Hoffner. 1997. DNA fingerprinting of Mycobacterium tuberculosis strains from patients with pulmonary tuberculosis in Honduras. J. Clin. Microbiol. 35: 2393 2397.
63. Rado, T. A.,, J. H. Bates,, H. W. Engel,, E. Mankiewicz,, T. Murohashi,, Y. Mizuguchi,, and L. Sula. 1975. World Health Organization studies on bacteriophage typing of mycobacteria. Subdivision of the species Mycobacterium tuberculosis. Am. Rev. Respir. Dis. 111: 459 468.
64. Ramos, M. C.,, H. Soini,, G. C. Roscanni,, M. Jaques,, M. C. Villares,, and J. M. Musser. 1999. Extensive cross contamination of specimens with Mycobacterium tuberculosis in a reference laboratory. J. Clin. Microbiol. 97: 916 919.
65.Sampson S., R. Warren, M. Richardson, G. van der Spuy, and P. van Helden. 2001. IS 6110 insertions in Mycobacterium tuberculosis: predominantly into coding regions. J. Clin. Microbiol. 39: 34233424.
66. Snider, D. E., Jr.,, G. D. Kelly,, G. M. Cauthen,, N. J. Thompson,, and J. O. Kilburn. 1985. Infection and disease among contacts of tuberculosis cases with drug-resistant and drugsusceptible bacilli. Am. Rev. Respir. Dis. 13: 125 132.
67. Small, P. M.,, R. W. Shafer,, P. C. Hopewell,, S. P. Singh,, M. J. Murphy,, and E. Desmond. 1993. Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection. N. Engl. J. Med. 328: 1137 1144.
68. Sreevatsan, S.,, X. Pan,, K. E. Stockbauer,, N. D. Connell,, B. N. Kreiswirth,, T. S. Whittam,, and J. M Musser. 1997. Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionary recent global dissemination. Proc. Natl. Acad. Sci. USA 94: 9869 9874.
69. Styblo, K. 1984. Epidemiology of Tuberculosis. VER Gustav Fischer Verlag, Jena, Germany.
70. Supply, P.,, S. Lesjean,, E. Savine,, K. Kremer,, D. van Soolingen,, and C. Locht. 2001. Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. J. Clin. Microbiol. 39: 3563 3571.
71. Supply, P.,, E. Mazars,, S. Lesjean,, V. Vincent,, B. Gicquel,, and C. Locht. 2000. Variable human minisatellite-like regions in the Mycobacterium tuberculosis genome. Mol. Microbiol. 36: 762 771.
72. Teixeira, L.,, M. D. Perkins,, J. L. Johnson,, R. Keller,, M. Palaci,, and V. do Valle Dettoni. 2001. Infection and disease among household contacts of patients with multidrug-resistant tuberculosis. Int. J. Tuberc. Lung Dis. 5: 321 328.
73. Thierry, D.,, M. D. Cave,, K. D. Eisenach,, J. C. Crawford,, J. H. Bates,, B. Gicquel,, and J. L. Guesdon. 1990. IS 6110, an IS-like element of the Mycobacterium tuberculosis complex. Nucleic Acids Res. 18: 188.>
74. Valway, S. E.,, M. P. Sanchez,, T. F. Shinnick,, I. Orme,, T. Agerton,, D. Hoy,, J. S. Jones,, H. Westmoreland,, and I. M. Onorato. 1998. An outbreak involving extensive transmission of a virulent strain of Mycobacterium tuberculosis. N. Engl. J. Med. 338: 633 639.
75. van Embden, J. D.,, T. van Gorkom,, K. Kremer,, R. Jansen,, B. A. van Der Zeijst,, and L. M. Schouls. 2000. Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. J. Bacteriol. 182: 2393 2401.
76. van Embden, J. D. A.,, M. D. Cave,, J. T. Crawford,, J. W. Dale,, K. D. Eisenach,, B. Gicquel,, P. Hermans,, C. Martin,, R. McAdam,, T. M. Shinnick,, and P. M. Small. 1993. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendation for a standardized methodology. J. Clin. Microbiol. 31: 406 409.
77.van Rie, A, R. Warren, M. Richardson, T. C. Victor, R. P. Gie, D. A. Enarson, N. Beyers, and P. D. van Helden. 1999. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N. Engl. J. Med. 341: 11741179.
78. van Soolingen, D.,, M. W. Borgdorff,, P. E. de Haas,, M. M. Sebek,, J. Veen,, M. Dessens, K. Kremer,, and J. D. van Embden. 1999. Molecular epidemiology of tuberculosis in the Netherlands: a nationwide study from 1993 through 1997. J. Infect. Dis. 18: 726 736.
79. van Soolingen, D.,, E. W. Petra,, P. de Haas,, P. Hermans,, P. Groenen,, and J. D. van Embden. 1993. Comparison of various repetitive DNA elements as generic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis. J. Clin. Microbiol. 31: 1987 1995.
80. van Soolingen, D.,, L. Qian,, P. E. de Haas,, J. T. Douglas,, H. Traore,, F. Portaels,, H. Z. Qing,, D. Enkhsaikan,, P. Nymadawa,, and J. D. van Embden. 1995. Predominance of a single genotype of Mycobacterium tuberculosis in countries of East Asia. J. Clin. Microbiol. 33: 3234 3243.
81. Vynnycky, E.,, N. Nagelkerke,, M. W. Borgdorff,, D. van Soolingen,, and J. D. van Embden. 2001. The effect of age and study duration on the relationship between “clustering” of DNA fingerprint patterns and the proportion of tuberculosis disease attributable to recent transmission. Epidemiol. Infect. 126: 43 62.
82. Warren, R.,, M. Richardson,, G. van der Spuy,, T. Victor,, S. Sampson,, N. Beyers,, and P. van Helden. 1999. DNA fingerprinting and molecular epidemiology of tuberculosis: use and interpretation in an epidemic setting. Electrophoresis 20: 1807 1812.
83. Wilkinson, D.,, M. Pillay,, J. Crump,, C. Lombard,, G. R. Davies,, and A. W. Sturm. 1997. Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in rural Africa. Trop. Med. Int. Health 2: 747 753.
84. Yang, Z.,, P. F. Barnes,, F. Chaves,, K. D. Eisenach,, S. Weis,, J. H. Bates,, and M. D. Cave. 1998. Diversity of DNA fingerprints of Mycobacterium tuberculosis isolates in the United States. J. Clin. Microbiol. 36: 1003 1007.
85. Yang, Z. H.,, K. Ijaz,, J. H. Bates,, K. D. Eisenach,, and M. D. Cave. 2000. Spoligotyping and PGRS fingerprinting of Mycobacterium tuberculosis strains having few copies of IS 6110. J. Clin Microbiol. 38: 3572 3576.
86. Yang, Z. H.,, A. Rendon,, A. Flores,, R. Medina,, K. Ijaz,, J. Llaca,, K. D. Eisenach,, J. H. Bates,, A. Villareal,, and M. D. Cave. 2000. A clinic-based molecular epidemiologic study of tuberculosis in Monterrey, Mexico. Int. J. Tuberc. Lung Dis. 5: 313 320.
87. Zhang, M.,, J. Gong,, Z. Yang,, B. Samten,, M. D. Cave,, and P. F. Barnes. 1999. Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in macrophages. J. Infect. Dis. 179: 1213 1217.
88. Zhang, Y.,, B. Heym,, B. Allen,, D. Young,, and S. Cole. 1992. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358: 591 593.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error