Abstract
Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to the global control of the disease. The purpose of this study was to characterize MDR-TB patients from Poland and to determine the extent of MDR-TB disease attributable to recent transmission. The study included all 46 patients diagnosed with MDR-TB in Poland in 2004 and followed up for 6 years (until 2011). For each patient, sociodemographic and clinical characteristics, treatment outcomes, and bacteriological data were collected by the review of medical and laboratory records. Mycobacterium tuberculosis isolates from all patients were characterized using spoligotyping, mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing, IS6110 restriction fragment length polymorphism (RFLP) analysis, and sequencing analysis of drug resistance-associated loci (katG, mabA-inhA, rpoβ, rpsL, and embB). The majority of patients were male (86.9 %), 40–64 years of age (60.8 %), with a history of TB treatment (84.8 %), and producing smear-positive sputa (86.9 %). Twenty-two (47.8 %) patients suffered from concomitant diseases and 28 (60.8 %) were alcohol abusers. Treatment outcome assessment revealed that 8 (17.4 %) patients were cured or completed therapy, while 15 (32.6 %) died of TB, 11 (23.9 %) defaulted, 8 (17.4 %) failed, and 1 (2.2 %) was transferred and lost to follow-up. Upon genotyping, 10 (21.7 %) isolates were allocated in four clusters. These were further subdivided by mutational profiling. Overall, in 6 (13 %) patients, MDR-TB was a result of recent transmission. For 4 (8.7 %) of these patients, a direct epidemiological link was established. The study shows that the transmission of MDR-TB occurs at a low rate in Poland. Of urgent need is the implementation of a policy of enforced treatment of MDR-TB patients in Poland.
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References
World Health Organization (WHO) (2012) Global tuberculosis control: surveillance, planning, financing. WHO, Geneva. WHO/HTM/TB/2012.6
Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, van Soolingen D, Jensen P, Bayona J (2010) Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet 375:1830–1843
World Health Organization (WHO) (2010) Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 global report on surveillance and response. WHO, Geneva. WHO/HTM/TB/2010.3
Jagielski T, Augustynowicz-Kopec E, Zozio T, Rastogi N, Zwolska Z (2010) Spoligotype-based comparative population structure analysis of multidrug-resistant and isoniazid-monoresistant Mycobacterium tuberculosis complex clinical isolates in Poland. J Clin Microbiol 48:3899–3909
European Centre for Disease Prevention and Control (ECDC)/World Health Organization Regional Office for Europe (2012) Surveillance report. Tuberculosis surveillance and monitoring in Europe 2012. ECDC, Stockholm
Casal M, Vaquero M, Rinder H, Tortoli E, Grosset J, Rüsch-Gerdes S, Gutiérrez J, Jarlier V (2005) A case–control study for multidrug-resistant tuberculosis: risk factors in four European countries. Microb Drug Resist 11:62–67
Faustini A, Hall AJ, Perucci CA (2006) Risk factors for multidrug resistant tuberculosis in Europe: a systematic review. Thorax 61:158–163
Suárez-García I, Rodríguez-Blanco A, Vidal-Pérez JL, García-Viejo MA, Jaras-Hernández MJ, López O, Noguerado-Asensio A (2009) Risk factors for multidrug-resistant tuberculosis in a tuberculosis unit in Madrid, Spain. Eur J Clin Microbiol Infect Dis 28:325–330
Zhao M, Li X, Xu P, Shen X, Gui X, Wang L, Deriemer K, Mei J, Gao Q (2009) Transmission of MDR and XDR tuberculosis in Shanghai, China. PLoS One 4:e4370
Moonan PK, Teeter LD, Salcedo K, Ghosh S, Ahuja SD, Flood J, Graviss EA (2013) Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study. Lancet Infect Dis 13:777–784
Leung EC, Leung CC, Kam KM, Yew WW, Chang KC, Leung WM, Tam CM (2013) Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city. Eur Respir J 41:901–908
Pfyffer GE, Bonato DA, Ebrahimzadeh A, Gross W, Hotaling J, Kornblum J, Laszlo A, Roberts G, Salfinger M, Wittwer F, Siddiqi S (1999) Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial drugs by using the radiometric BACTEC 460 technique and the proportion method with solid media. J Clin Microbiol 37:3179–3186
World Health Organization (WHO) (2008) Policy guidance on drug-susceptibility testing (DST) of second-line antituberculosis drugs. WHO, Geneva. WHO/HTM/TB/2008.392
van Embden JDA, Cave MD, Crawford JT, Dale JW, Eisenach KD, Gicquel B, Hermans P, Martin C, McAdam R, Shinnick TM, Small PM (1993) Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 31:406–409
Supply P (2005) Multilocus variable number tandem repeat genotyping of Mycobacterium tuberculosis. Technical guide. Institut de Biologie/Institut Pasteur de Lille. Available online at: http://www.miru-vntrplus.org/MIRU/files/MIRU-VNTRtypingmanualv6.pdf
Ferrara G, Richeldi L, Bugiani M, Cirillo D, Besozzi G, Nutini S, Casali L, Fiorentini F, Codecasa LR, Migliori GB (2005) Management of multidrug-resistant tuberculosis in Italy. Int J Tuberc Lung Dis 9:507–513
Vázquez-Gallardo R, Anibarro L, Fernández-Villar A, Díaz-Cabanela D, Cruz-Ferro E, Pérez del Molino ML, Túñez V, Samper S, Iglesias MJ (2007) Multidrug-resistant tuberculosis in a low-incidence region shows a high rate of transmission. Int J Tuberc Lung Dis 11:429–435
Story A, Murad S, Roberts W, Verheyen M, Hayward AC; London Tuberculosis Nurses Network (2007) Tuberculosis in London: the importance of homelessness, problem drug use and prison. Thorax 62:667–671
Brzezińska S, Zabost A, Kozińska M, Janicka-Sobierajska G, Zwolska Z, Augustynowicz-Kopeć E (2012) Molecular analysis of strains from tuberculosis patients in Polish prisons in 2004–2008. Initial analysis of the project. Pneumonol Alergol Pol 80:209–213
Fisher-Hoch SP, Whitney E, McCormick JB, Crespo G, Smith B, Rahbar MH, Restrepo BI (2008) Type 2 diabetes and multidrug-resistant tuberculosis. Scand J Infect Dis 40:888–893
Gelmanova IY, Keshavjee S, Golubchikova VT, Berezina VI, Strelis AK, Yanova GV, Atwood S, Murray M (2007) Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance. Bull World Health Organ 85:703–711
Devaux I, Manissero D, Fernandez de la Hoz K, Kremer K, van Soolingen D; EuroTB network (2010) Surveillance of extensively drug-resistant tuberculosis in Europe, 2003–2007. Euro Surveill 15:19518
Uffredi ML, Truffot-Pernot C, Dautzenberg B, Renard M, Jarlier V, Robert J (2007) An intervention programme for the management of multidrug-resistant tuberculosis in France. Int J Antimicrob Agents 29:434–439
Eker B, Ortmann J, Migliori GB, Sotgiu G, Muetterlein R, Centis R, Hoffmann H, Kirsten D, Schaberg T, Ruesch-Gerdes S, Lange C; German TBNET Group (2008) Multidrug- and extensively drug-resistant tuberculosis, Germany. Emerg Infect Dis 14:1700–1706
Narita M, Alonso P, Lauzardo M, Hollender ES, Pitchenik AE, Ashkin D (2001) Treatment experience of multidrug-resistant tuberculosis in Florida, 1994–1997. Chest 120:343–348
Kliiman K, Altraja A (2009) Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB. Eur Respir J 33:1085–1094
Migliori GB, Lange C, Centis R, Sotgiu G, Mütterlein R, Hoffmann H, Kliiman K, De Iaco G, Lauria FN, Richardson MD, Spanevello A, Cirillo DM; TBNET Study Group (2008) Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases. Eur Respir J 31:1155–1159
Leimane V, Dravniece G, Riekstina V, Sture I, Kammerer S, Chen MP, Skenders G, Holtz TH (2010) Treatment outcome of multidrug/extensively drug-resistant tuberculosis in Latvia, 2000–2004. Eur Respir J 36:584–593
Chiang CY, Enarson DA, Yu MC, Bai KJ, Huang RM, Hsu CJ, Suo J, Lin TP (2006) Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study. Eur Respir J 28:980–985
Franke MF, Appleton SC, Bayona J, Arteaga F, Palacios E, Llaro K, Shin SS, Becerra MC, Murray MB, Mitnick CD (2008) Risk factors and mortality associated with default from multidrug-resistant tuberculosis treatment. Clin Infect Dis 46:1844–1851
van Doorn HR, de Haas PE, Kremer K, Vandenbroucke-Grauls CM, Borgdorff MW, van Soolingen D (2006) Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands. Clin Microbiol Infect 12:769–775
Verhagen LM, van den Hof S, van Deutekom H, Hermans PW, Kremer K, Borgdorff MW, van Soolingen D (2011) Mycobacterial factors relevant for transmission of tuberculosis. J Infect Dis 203:1249–1255
Ghebremichael S, Petersson R, Koivula T, Pennhag A, Romanus V, Berggren I, Petrini B, Hoffner S, Källenius G (2008) Molecular epidemiology of drug-resistant tuberculosis in Sweden. Microbes Infect 10:699–705
Ködmön C, Niemann S, Lukács J, Sör E, Dávid S, Somoskövi A (2006) Molecular epidemiology of drug-resistant tuberculosis in Hungary. J Clin Microbiol 44:4258–4261
Moro ML, Salamina G, Gori A, Penati V, Sacchetti R, Mezzetti F, Infuso A, Sodano L (2002) Two-year population-based molecular epidemiological study of tuberculosis transmission in the metropolitan area of Milan, Italy. Eur J Clin Microbiol Infect Dis 21:114–122
Munsiff SS, Bassoff T, Nivin B, Li J, Sharma A, Bifani P, Mathema B, Driscoll J, Kreiswirth BN (2002) Molecular epidemiology of multidrug-resistant tuberculosis, New York City, 1995–1997. Emerg Infect Dis 8:1230–1238
Perdigão J, Macedo R, João I, Fernandes E, Brum L, Portugal I (2008) Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective. Microb Drug Resist 14:133–143
Nitta AT, Knowles LS, Kim J, Lehnkering EL, Borenstein LA, Davidson PT, Harvey SM, De Koning ML (2002) Limited transmission of multidrug-resistant tuberculosis despite a high proportion of infectious cases in Los Angeles County, California. Am J Respir Crit Care Med 165:812–817
Jagielski T, van Ingen J, Rastogi N, Dziadek J, Mazur PK, Bielecki J (2014) Current methods in the molecular typing of Mycobacterium tuberculosis and other mycobacteria. BioMed Research Intern 2014:645802
Hazbón MH, Brimacombe M, Bobadilla del Valle M, Cavatore M, Guerrero MI, Varma-Basil M, Billman-Jacobe H, Lavender C, Fyfe J, García-García L, León CI, Bose M, Chaves F, Murray M, Eisenach KD, Sifuentes-Osornio J, Cave MD, Ponce de León A, Alland D (2006) Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 50:2640–2649
Jagielski T, Bakuła Z, Roeske K, Kamiński M, Napiórkowska A, Augustynowicz-Kopeć E, Zwolska Z, Bielecki J (2014) Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates. J Antimicrob Chemother. doi:10.1093/jac/dku161
Jagielski T, Ignatowska H, Bakuła Z, Dziewit L, Napiórkowska A, Augustynowicz-Kopeć E, Zwolska Z, Bielecki J (2014) Screening for streptomycin resistance-conferring mutations in Mycobacterium tuberculosis clinical isolates from Poland. PLoS One 9:e100078
Bakuła Z, Napiórkowska A, Bielecki J, Augustynowicz-Kopeć E, Zwolska Z, Jagielski T (2013) Mutations in the embB gene and their association with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates from Poland. Biomed Res Int 2013:167954
Acknowledgments
The authors are greatly indebted to the heads and staff of the regional TB laboratories, in particular to Maria Bełzowska (Wrocław), Mirosława Dąbrowska (Lublin), Łucja Filipczyk (Katowice), Hanna Górecka (Nowy Sącz), Maria Janiak (Nowy Sącz), Maria Kowalska (Otwock), Dorota Krawiecka (Bydgoszcz), Joanna Łukaszewicz (Białystok), Bożena Malinowska (Kielce), Elżbieta Naparta-Kapusta (Łódź), Grażyna Passak-Stańda (Kraków), Bożena Piskuła (Szczecin), Danuta Przytocka (Wrocław), Alicja Sankowska (Gdańsk), Krzysztof Skłodowski (Kowary), Teresa Tarnawska (Częstochowa), and Beata Żmudzin (Rudka), for their excellent help in the collection and interpretation of the clinical and microbiological data concerning patients evaluated in this study.
Special thanks are extended to the clinicians of the regional TB dispensaries and other medical facilities, in particular to Magdalena Biernat-Silczuk (Kraków), Piotr Cichoń (Lubliniec), Jerzy Czyż (Rybnik), Jan Juchacki (Jędrzejów), Małgorzata Jurdyga (Kowary), Krystyna Kaczorowska-Polakiewicz (Nowy Sącz), Lidia Kościółko-Fałkowska (Biłgoraj), Maria Lewandowska-Holewik (Kowary), Małgorzata Kwiatkowska (Bełżyce), Maria Michalska (Jaroszowiec), Beata Michna (Kraków), Hanna Owczarzak (Bydgoszcz), Barbara Patora-Eger (Łódź), Izabela Piętowska-Łazuka (Parczew), Elżbieta Poniatowska-Kubina (Zamość), Hanna Potoczna (Lublin), Bronisław Prystupa (Łęczna), Elżbieta Smaga-Pawluk (Lublin), Anna Szydłowska (Puławy), Mirosława Tałałaj (Sokółka), and Marek Zakościelny (Kraśnik), for providing patients’ medical documentation and for the information on their present situation.
The work was partially financed by the Iuventus Plus grant from the Polish Ministry of Science and Higher Education (contract no. IP2011018771). No additional external funding was received for this study.
Part of the results concerning mutational analysis of the isoniazid, streptomycin, and ethambutol resistance-associated loci have already been published elsewhere [41–43].
Conflict of interest
The authors declare that they have no competing interests. Alex van Belkum is currently working for bioMérieux, a company developing and selling infectious disease diagnostics.
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Supplementary Table 1
Primers used for PCR amplification and sequencing of drug resistance-associated genes. (DOCX 18 kb)
Supplementary Table 2
Mutations detected in five genetic loci among 46 MDR M. tuberculosis isolates. (DOCX 18 kb)
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Jagielski, T., Brzostek, A., van Belkum, A. et al. A close-up on the epidemiology and transmission of multidrug-resistant tuberculosis in Poland. Eur J Clin Microbiol Infect Dis 34, 41–53 (2015). https://doi.org/10.1007/s10096-014-2202-z
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DOI: https://doi.org/10.1007/s10096-014-2202-z