Abstract
The epidemiological relatedness of drug-resistant Mycobacterium tuberculosis strains isolated in Germany in 1995 was evaluated by the standardized IS6110 fingerprinting method. Altogether, 196 M. tuberculosis isolates from 167 patients were analyzed. A large degree of IS6110 polymorphism was found, ranging from 1 to 20 copies. Multiple isolates from one patient generally remained stable over a period of up to 1 year. However, one strain showed an additional fragment 7 months after the first isolate was obtained. Isolates from 55 patients (33%) showed identical fingerprint patterns or fingerprint patterns that differed only in one band, and thus they were clustered in 22 fingerprint groups. Specific transmission links could be established between members of four groups, e.g., transmission by family contacts. In one case, transmission of a multidrug-resistant strain to a patient initially infected with a drug-susceptible strain could be shown. Besides these fingerprint groups, 30 of the 167 isolates (approximately 18%) could be grouped in two fingerprint clusters with a similarity of at least 78%. Approximately 60% of the patients of these two clusters were known to be immigrants from the former Soviet Union, and one patient is still living in Belarus. In conclusion, our results indicate that (i) transmission of drug-resistant strains contributes substantially to the emergence of drug-resistant tuberculosis in Germany and (ii) drug-resistant M. tuberculosis strains were presumably carried over from the former Soviet Union to Germany by immigrants.
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- Alland D., Kalkut G. E., Moss A. R., McAdam R. A., Hahn J. A., Bosworth W., Drucker E., Bloom B. R. Transmission of tuberculosis in New York City. An analysis by DNA fingerprinting and conventional epidemiologic methods. N Engl J Med. 1994 Jun 16;330(24):1710–1716. doi: 10.1056/NEJM199406163302403. [DOI] [PubMed] [Google Scholar]
- Aznar J., Safi H., Romero J., Alejo A., Gracia A., Palomares J. C. Nosocomial transmission of tuberculosis infection in pediatrics wards. Pediatr Infect Dis J. 1995 Jan;14(1):44–48. doi: 10.1097/00006454-199501000-00009. [DOI] [PubMed] [Google Scholar]
- Barnes P. F., el-Hajj H., Preston-Martin S., Cave M. D., Jones B. E., Otaya M., Pogoda J., Eisenach K. D. Transmission of tuberculosis among the urban homeless. JAMA. 1996 Jan 24;275(4):305–307. [PubMed] [Google Scholar]
- Cave M. D., Eisenach K. D., McDermott P. F., Bates J. H., Crawford J. T. IS6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting. Mol Cell Probes. 1991 Feb;5(1):73–80. doi: 10.1016/0890-8508(91)90040-q. [DOI] [PubMed] [Google Scholar]
- Demissie M., Gebeyehu M., Berhane Y. Primary resistance to anti-tuberculosis drugs in Addis Ababa, Ethiopia. Int J Tuberc Lung Dis. 1997 Feb;1(1):64–67. [PubMed] [Google Scholar]
- Edlin B. R., Tokars J. I., Grieco M. H., Crawford J. T., Williams J., Sordillo E. M., Ong K. R., Kilburn J. O., Dooley S. W., Castro K. G. An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992 Jun 4;326(23):1514–1521. doi: 10.1056/NEJM199206043262302. [DOI] [PubMed] [Google Scholar]
- Frieden T. R., Sterling T., Pablos-Mendez A., Kilburn J. O., Cauthen G. M., Dooley S. W. The emergence of drug-resistant tuberculosis in New York City. N Engl J Med. 1993 Feb 25;328(8):521–526. doi: 10.1056/NEJM199302253280801. [DOI] [PubMed] [Google Scholar]
- Genewein A., Telenti A., Bernasconi C., Mordasini C., Weiss S., Maurer A. M., Rieder H. L., Schopfer K., Bodmer T. Molecular approach to identifying route of transmission of tuberculosis in the community. Lancet. 1993 Oct 2;342(8875):841–844. doi: 10.1016/0140-6736(93)92698-s. [DOI] [PubMed] [Google Scholar]
- Gordin F. M., Nelson E. T., Matts J. P., Cohn D. L., Ernst J., Benator D., Besch C. L., Crane L. R., Sampson J. H., Bragg P. S. The impact of human immunodeficiency virus infection on drug-resistant tuberculosis. Am J Respir Crit Care Med. 1996 Nov;154(5):1478–1483. doi: 10.1164/ajrccm.154.5.8912768. [DOI] [PubMed] [Google Scholar]
- Goyal M., Ormerod L. P., Shaw R. J. Epidemiology of an outbreak of drug-resistant tuberculosis in the U.K. using restriction fragment length polymorphism. Clin Sci (Lond) 1994 Jun;86(6):749–751. doi: 10.1042/cs0860749. [DOI] [PubMed] [Google Scholar]
- Hermans P. W., Messadi F., Guebrexabher H., van Soolingen D., de Haas P. E., Heersma H., de Neeling H., Ayoub A., Portaels F., Frommel D. Analysis of the population structure of Mycobacterium tuberculosis in Ethiopia, Tunisia, and The Netherlands: usefulness of DNA typing for global tuberculosis epidemiology. J Infect Dis. 1995 Jun;171(6):1504–1513. doi: 10.1093/infdis/171.6.1504. [DOI] [PubMed] [Google Scholar]
- McAdam R. A., Hermans P. W., van Soolingen D., Zainuddin Z. F., Catty D., van Embden J. D., Dale J. W. Characterization of a Mycobacterium tuberculosis insertion sequence belonging to the IS3 family. Mol Microbiol. 1990 Sep;4(9):1607–1613. doi: 10.1111/j.1365-2958.1990.tb02073.x. [DOI] [PubMed] [Google Scholar]
- Mendoza M. T., Gonzaga A. J., Roa C., Velmonte M. A., Jorge M., Montoya J. C., Tan Torres T., Ong M., Barez M. Y., Ang C. F. Nature of drug resistance and predictors of multidrug-resistant tuberculosis among patients seen at the Philippine General Hospital, Manila, Philippines. Int J Tuberc Lung Dis. 1997 Feb;1(1):59–63. [PubMed] [Google Scholar]
- Nardell E., McInnis B., Thomas B., Weidhaas S. Exogenous reinfection with tuberculosis in a shelter for the homeless. N Engl J Med. 1986 Dec 18;315(25):1570–1575. doi: 10.1056/NEJM198612183152502. [DOI] [PubMed] [Google Scholar]
- Poulet S., Cole S. T. Repeated DNA sequences in mycobacteria. Arch Microbiol. 1995 Feb;163(2):79–86. doi: 10.1007/BF00381780. [DOI] [PubMed] [Google Scholar]
- Rigouts L., Kubín M., Havelková M., Portaels F. DNA fingerprint analysis of drug resistant Mycobacterium tuberculosis strains isolated in the Czech Republic. Cent Eur J Public Health. 1994 Jun;2(1):58–59. [PubMed] [Google Scholar]
- Rigouts L., Portaels F. Restriction fragment length polymorphism analysis of drug resistant Mycobacterium tuberculosis strains isolated in Belgium. Acta Clin Belg. 1994;49(1):5–11. doi: 10.1080/17843286.1994.11718356. [DOI] [PubMed] [Google Scholar]
- Saunders N. A. State of the art: typing Mycobacterium tuberculosis. J Hosp Infect. 1995 Mar;29(3):169–176. doi: 10.1016/0195-6701(95)90326-7. [DOI] [PubMed] [Google Scholar]
- Shafer R. W., Singh S. P., Larkin C., Small P. M. Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in an immunocompetent patient. Tuber Lung Dis. 1995 Dec;76(6):575–577. doi: 10.1016/0962-8479(95)90537-5. [DOI] [PubMed] [Google Scholar]
- Small P. M., Hopewell P. C., Singh S. P., Paz A., Parsonnet J., Ruston D. C., Schecter G. F., Daley C. L., Schoolnik G. K. The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods. N Engl J Med. 1994 Jun 16;330(24):1703–1709. doi: 10.1056/NEJM199406163302402. [DOI] [PubMed] [Google Scholar]
- Small P. M., McClenny N. B., Singh S. P., Schoolnik G. K., Tompkins L. S., Mickelsen P. A. Molecular strain typing of Mycobacterium tuberculosis to confirm cross-contamination in the mycobacteriology laboratory and modification of procedures to minimize occurrence of false-positive cultures. J Clin Microbiol. 1993 Jul;31(7):1677–1682. doi: 10.1128/jcm.31.7.1677-1682.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Small P. M., Shafer R. W., Hopewell P. C., Singh S. P., Murphy M. J., Desmond E., Sierra M. F., Schoolnik G. K. Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection. N Engl J Med. 1993 Apr 22;328(16):1137–1144. doi: 10.1056/NEJM199304223281601. [DOI] [PubMed] [Google Scholar]
- Sola C., Horgen L., Goh K. S., Rastogi N. Molecular fingerprinting of Mycobacterium tuberculosis on a Caribbean island with IS6110 and DRr probes. J Clin Microbiol. 1997 Apr;35(4):843–846. doi: 10.1128/jcm.35.4.843-846.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strässle A., Putnik J., Weber R., Fehr-Merhof A., Wüst J., Pfyffer G. E. Molecular epidemiology of Mycobacterium tuberculosis strains isolated from patients in a human immunodeficiency virus cohort in Switzerland. J Clin Microbiol. 1997 Feb;35(2):374–378. doi: 10.1128/jcm.35.2.374-378.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thierry D., Brisson-Noël A., Vincent-Lévy-Frébault V., Nguyen S., Guesdon J. L., Gicquel B. Characterization of a Mycobacterium tuberculosis insertion sequence, IS6110, and its application in diagnosis. J Clin Microbiol. 1990 Dec;28(12):2668–2673. doi: 10.1128/jcm.28.12.2668-2673.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Torrea G., Levee G., Grimont P., Martin C., Chanteau S., Gicquel B. Chromosomal DNA fingerprinting analysis using the insertion sequence IS6110 and the repetitive element DR as strain-specific markers for epidemiological study of tuberculosis in French Polynesia. J Clin Microbiol. 1995 Jul;33(7):1899–1904. doi: 10.1128/jcm.33.7.1899-1904.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Versalovic J., Kapur V., Koeuth T., Mazurek G. H., Whittam T. S., Musser J. M., Lupski J. R. DNA fingerprinting of pathogenic bacteria by fluorophore-enhanced repetitive sequence-based polymerase chain reaction. Arch Pathol Lab Med. 1995 Jan;119(1):23–29. [PubMed] [Google Scholar]
- Warren R., Hauman J., Beyers N., Richardson M., Schaaf H. S., Donald P., van Helden P. Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community. S Afr Med J. 1996 Jan;86(1):45–49. [PubMed] [Google Scholar]
- Yang Z. H., de Haas P. E., Wachmann C. H., van Soolingen D., van Embden J. D., Andersen A. B. Molecular epidemiology of tuberculosis in Denmark in 1992. J Clin Microbiol. 1995 Aug;33(8):2077–2081. doi: 10.1128/jcm.33.8.2077-2081.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Embden J. D., Cave M. D., Crawford J. T., Dale J. W., Eisenach K. D., Gicquel B., Hermans P., Martin C., McAdam R., Shinnick T. M. Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol. 1993 Feb;31(2):406–409. doi: 10.1128/jcm.31.2.406-409.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Soolingen D., Hermans P. W., de Haas P. E., Soll D. R., van Embden J. D. Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol. 1991 Nov;29(11):2578–2586. doi: 10.1128/jcm.29.11.2578-2586.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Soolingen D., de Haas P. E., Hermans P. W., Groenen P. M., van Embden J. D. Comparison of various repetitive DNA elements as genetic markers for strain differentiation and epidemiology of Mycobacterium tuberculosis. J Clin Microbiol. 1993 Aug;31(8):1987–1995. doi: 10.1128/jcm.31.8.1987-1995.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]