Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda

English version

Autoři: Eddie M. Wampande ^aff001; Peter Naniima ^aff001; Ezekiel Mupere ^aff003; David P. Kateete ^aff001; LaShaunda L. Malone ^aff004; Catherine M. Stein ^aff005; Harriet Mayanja-Kizza ^aff004; Sebastien Gagneux ^aff007; W. Henry Boom ^aff005; Moses L. Joloba ^aff001
Působiště autorů: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda ^aff001; Department of Veterinary Medicine, Clinical and Comparative medicine, College of Veterinary Medicine, Animal Resources and Bio Security, Makerere University, Kampala, Uganda ^aff002; Department of Pediatrics and Child Health College of Health Sciences, Makerere University, Kampala, Uganda ^aff003; Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda ^aff004; Tuberculosis Research Unit, School of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, Uinted States of America ^aff005; Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, Uinted States of America ^aff006; Swiss Tropical and Public Health Institute, Basel, Switzerland ^aff007; University of Basel, Basel, Switzerland ^aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0221644

Souhrn

Background

Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes.

Method

A total of 141 M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat (DR) loci for all the isolates was examined for sub-lineage specific signatures as described in the SITVIT2 database. The infecting sub-strains were matched with patients’ clinical and demographic characteristics to identify any possible association.

Result

The data showed 3 sub-lineages circulating with CAS 1 Delhi accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether the sub-lineages differ in their ability to cause increased severe disease, we used extent of lung involvement as a proxy for severe disease. Multivariable analysis showed no association between M. tuberculosis lineage 3 sub-lineages with severe disease. The risk factors associated with severe disease include having a positive smear (OR = 9.384; CI 95% = 2.603–33.835), HIV (OR = 0.316; CI 95% = 0.114–0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034–0.856) and a BCG scar (OR = 0.295; CI 95% = 0.102–0.854).

Conclusion

In Kampala, Uganda, there are three sub-lineages of M. tuberculosis lineage 3 that cause disease of comparable severity with CAS-Dehli as the most prevalent. Having HIV, lymphadenitis, a BCG scar and a smear negative status is associated with reduced severe disease.

Klíčová slova:

Biology and life sciences – Organisms – People and places – Geographical locations – Anatomy – Medicine and health sciences – Microbiology – Medical microbiology – Microbial pathogens – Bacteria – Pathology and laboratory medicine – Pathogens – Physiology – Diagnostic medicine – Signs and symptoms – Africa – Infectious diseases – Bacterial diseases – Tuberculosis – Tropical diseases – Viral pathogens – Immunodeficiency viruses – HIV – Retroviruses – Lentivirus – Viruses – RNA viruses – Actinobacteria – Mycobacterium tuberculosis – Body fluids – Blood – Physiological processes – Extensively drug-resistant tuberculosis – Epidemiology – Medical risk factors – Coughing – Uganda

Zdroje

1. Brites D, Gagneux S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunological reviews. 2015;264(1):6–24. doi: 10.1111/imr.12264 25703549; PubMed Central PMCID: PMC4339235.

2. Firdessa R, Berg S, Hailu E, Schelling E, Gumi B, Erenso G, et al. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerging infectious diseases. 2013;19(3):460–3. doi: 10.3201/eid1903.120256 23622814; PubMed Central PMCID: PMC3647644.

3. Coscolla M, Gagneux S. Consequences of genomic diversity in Mycobacterium tuberculosis. Seminars in immunology. 2014;26(6):431–44. doi: 10.1016/j.smim.2014.09.012 25453224; PubMed Central PMCID: PMC4314449.

4. Gagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC, Narayanan S, et al. Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(8):2869–73. doi: 10.1073/pnas.0511240103 16477032; PubMed Central PMCID: PMC1413851.

5. Gagneux S, Small PM. Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. The Lancet Infectious diseases. 2007;7(5):328–37. doi: 10.1016/S1473-3099(07)70108-1 17448936.

6. Comas I, Homolka S, Niemann S, Gagneux S. Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PloS one. 2009;4(11):e7815. doi: 10.1371/journal.pone.0007815 19915672; PubMed Central PMCID: PMC2772813.

7. Wampande EM, Hatzios SK, Achan B, Mupere E, Nsereko M, Mayanja HK, et al. A single-nucleotide-polymorphism real-time PCR assay for genotyping of Mycobacterium tuberculosis complex in peri-urban Kampala. BMC infectious diseases. 2015;15:396. doi: 10.1186/s12879-015-1121-7 26423522; PubMed Central PMCID: PMC4590274.

8. Brudey K, Driscoll JR, Rigouts L, Prodinger WM, Gori A, Al-Hajoj SA, et al. Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC microbiology. 2006;6:23. doi: 10.1186/1471-2180-6-23 16519816; PubMed Central PMCID: PMC1468417.

9. Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nature genetics. 2013;45(10):1176–82. doi: 10.1038/ng.2744 23995134; PubMed Central PMCID: PMC3800747.

10. Brites D, Gagneux S. Old and new selective pressures on Mycobacterium tuberculosis. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2012;12(4):678–85. doi: 10.1016/j.meegid.2011.08.010 21867778; PubMed Central PMCID: PMC3253320.

11. Wampande EM, Mupere E, Debanne SM, Asiimwe BB, Nsereko M, Mayanja H, et al. Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease. BMC infectious diseases. 2013;13:484. doi: 10.1186/1471-2334-13-484 24134504; PubMed Central PMCID: PMC3853102.

12. Parwati I, van Crevel R, van Soolingen D. Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains. The Lancet Infectious diseases. 2010;10(2):103–11. doi: 10.1016/S1473-3099(09)70330-5 20113979.

13. Ordway D, Henao-Tamayo M, Shanley C, Smith EE, Palanisamy G, Wang B, et al. Influence of Mycobacterium bovis BCG vaccination on cellular immune response of guinea pigs challenged with Mycobacterium tuberculosis. Clinical and vaccine immunology: CVI. 2008;15(8):1248–58. doi: 10.1128/CVI.00019-08 18508930; PubMed Central PMCID: PMC2519313.

14. Ordway DJ, Shang S, Henao-Tamayo M, Obregon-Henao A, Nold L, Caraway M, et al. Mycobacterium bovis BCG-mediated protection against W-Beijing strains of Mycobacterium tuberculosis is diminished concomitant with the emergence of regulatory T cells. Clinical and vaccine immunology: CVI. 2011;18(9):1527–35. doi: 10.1128/CVI.05127-11 21795460; PubMed Central PMCID: PMC3165219.

15. Kato-Maeda M, Shanley CA, Ackart D, Jarlsberg LG, Shang S, Obregon-Henao A, et al. Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig. Clinical and vaccine immunology: CVI. 2012;19(8):1227–37. doi: 10.1128/CVI.00250-12 22718126; PubMed Central PMCID: PMC3416080.

16. Coscolla M, Gagneux S. Does M. tuberculosis genomic diversity explain disease diversity? Drug discovery today Disease mechanisms. 2010;7(1):e43–e59. doi: 10.1016/j.ddmec.2010.09.004 21076640; PubMed Central PMCID: PMC2976975.

17. Lukoye D, Katabazi FA, Musisi K, Kateete DP, Asiimwe BB, Okee M, et al. The T2 Mycobacterium tuberculosis genotype, predominant in Kampala, Uganda, shows negative correlation with antituberculosis drug resistance. Antimicrobial agents and chemotherapy. 2014;58(7):3853–9. doi: 10.1128/AAC.02338-13 24777100; PubMed Central PMCID: PMC4068514.

18. Newton SM, Smith RJ, Wilkinson KA, Nicol MP, Garton NJ, Staples KJ, et al. A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(42):15594–8. doi: 10.1073/pnas.0604283103 17028173; PubMed Central PMCID: PMC1622867.

19. Stucki D, Brites D, Jeljeli L, Coscolla M, Liu Q, Trauner A, et al. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages. Nature genetics. 2016;48(12):1535–43. doi: 10.1038/ng.3704 27798628; PubMed Central PMCID: PMC5238942.

20. Hershberg R. Human host range of Mycobacterium tuberculosis. Nature genetics. 2016;48(12):1453–4. doi: 10.1038/ng.3724 27898082

21. Stein CM, Zalwango S, Malone LL, Thiel B, Mupere E, Nsereko M, et al. Resistance and Susceptibility to Mycobacterium tuberculosis Infection and Disease in Tuberculosis Households in Kampala, Uganda. American journal of epidemiology. 2018;187(7):1477–89. doi: 10.1093/aje/kwx380 29304247; PubMed Central PMCID: PMC6031055.

22. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. Journal of clinical microbiology. 1997;35(4):907–14. 9157152; PubMed Central PMCID: PMC229700.

23. Couvin D, David A, Zozio T, Rastogi N. Macro-geographical specificities of the prevailing tuberculosis epidemic as seen through SITVIT2, an updated version of the Mycobacterium tuberculosis genotyping database. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2018. doi: 10.1016/j.meegid.2018.12.030 30593925.

24. Falk AP P.C. Classification of pulmonary tuberculosis. Diagnosis standards and classification of tuberculosis. Edited by: Falk A, O'Connor AJB, Pratt PC, Webb JA, Weir JA, Wolinsky A. 1969, New York, NY: National Tuberculosis and Respiratory Disease Association, 12: 68–76.

25. Asiimwe BB, Ghebremichael S, Kallenius G, Koivula T, Joloba ML. Mycobacterium tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in peri-urban Kampala, Uganda. BMC infectious diseases. 2008;8:101. doi: 10.1186/1471-2334-8-101 PubMed Central PMCID: PMC2519071. 18662405

26. Bazira J, Asiimwe BB, Joloba ML, Bwanga F, Matee MI. Mycobacterium tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in South-Western Uganda. BMC infectious diseases. 2011;11:81. doi: 10.1186/1471-2334-11-81 21453482; PubMed Central PMCID: PMC3100262.

27. Wamala D, Okee M, Kigozi E, Couvin D, Rastogi N, Joloba M, et al. Predominance of Uganda genotype of Mycobacterium tuberculosis isolated from Ugandan patients with tuberculous lymphadenitis. BMC research notes. 2015;8:398. doi: 10.1186/s13104-015-1362-y 26323435; PubMed Central PMCID: PMC4556223.

28. Asiimwe BB, Koivula T, Kallenius G, Huard RC, Ghebremichael S, Asiimwe J, et al. Mycobacterium tuberculosis Uganda genotype is the predominant cause of TB in Kampala, Uganda. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease. 2008;12(4):386–91. 18371263.

29. Dickman KR, Nabyonga L, Kateete DP, Katabazi FA, Asiimwe BB, Mayanja HK, et al. Detection of multiple strains of Mycobacterium tuberculosis using MIRU-VNTR in patients with pulmonary tuberculosis in Kampala, Uganda. BMC infectious diseases. 2010;10:349. doi: 10.1186/1471-2334-10-349 21143966; PubMed Central PMCID: PMC3004912.

30. Tanveer M, Hasan Z, Kanji A, Hussain R, Hasan R. Reduced TNF-alpha and IFN-gamma responses to Central Asian strain 1 and Beijing isolates of Mycobacterium tuberculosis in comparison with H37Rv strain. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2009;103(6):581–7. doi: 10.1016/j.trstmh.2009.03.014 19375139.

31. Chatterjee A, D'Souza D, Vira T, Bamne A, Ambe GT, Nicol MP, et al. Strains of Mycobacterium tuberculosis from western Maharashtra, India, exhibit a high degree of diversity and strain-specific associations with drug resistance, cavitary disease, and treatment failure. Journal of clinical microbiology. 2010;48(10):3593–9. doi: 10.1128/JCM.00430-10 20720028; PubMed Central PMCID: PMC2953068.

32. Malik AN, Godfrey-Faussett P. Effects of genetic variability of Mycobacterium tuberculosis strains on the presentation of disease. The Lancet Infectious diseases. 2005;5(3):174–83. doi: 10.1016/S1473-3099(05)01310-1 15766652.

33. Aderaye G, Bruchfeld J, Assefa G, Feleke D, Kallenius G, Baat M, et al. The relationship between disease pattern and disease burden by chest radiography, M. tuberculosis Load, and HIV status in patients with pulmonary tuberculosis in Addis Ababa. Infection. 2004;32(6):333–8. doi: 10.1007/s15010-004-3089-x 15597222.

34. Altet-Gomez MN, Alcaide J, Godoy P, Romero MA, Hernandez del Rey I. Clinical and epidemiological aspects of smoking and tuberculosis: a study of 13,038 cases. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease. 2005;9(4):430–6. 15830749.

35. Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2014;58(4):470–80. doi: 10.1093/cid/cit790 24336911.

36. Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. Bmj. 2014;349:g4643. doi: 10.1136/bmj.g4643 25097193; PubMed Central PMCID: PMC4122754.

37. van Soolingen D, Qian L, de Haas PE, Douglas JT, Traore H, Portaels F, et al. Predominance of a single genotype of Mycobacterium tuberculosis in countries of east Asia. Journal of clinical microbiology. 1995;33(12):3234–8. 8586708; PubMed Central PMCID: PMC228679.

38. Lopez B, Aguilar D, Orozco H, Burger M, Espitia C, Ritacco V, et al. A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes. Clinical and experimental immunology. 2003;133(1):30–7. doi: 10.1046/j.1365-2249.2003.02171.x 12823275; PubMed Central PMCID: PMC1808750.

39. Click ES, Moonan PK, Winston CA, Cowan LS, Oeltmann JE. Relationship between Mycobacterium tuberculosis phylogenetic lineage and clinical site of tuberculosis. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2012;54(2):211–9. doi: 10.1093/cid/cir788 22198989.

40. Srilohasin P, Chaiprasert A, Tokunaga K, Nishida N, Prammananan T, Smittipat N, et al. Genetic diversity and dynamic distribution of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Thailand. Journal of clinical microbiology. 2014;52(12):4267–74. doi: 10.1128/JCM.01467-14 25297330; PubMed Central PMCID: PMC4313297.

41. Caws M, Thwaites G, Dunstan S, Hawn TR, Lan NT, Thuong NT, et al. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS pathogens. 2008;4(3):e1000034. doi: 10.1371/journal.ppat.1000034 18369480; PubMed Central PMCID: PMC2268004.

42. Albanna AS, Reed MB, Kotar KV, Fallow A, McIntosh FA, Behr MA, et al. Reduced transmissibility of East African Indian strains of Mycobacterium tuberculosis. PloS one. 2011;6(9):e25075. doi: 10.1371/journal.pone.0025075 21949856; PubMed Central PMCID: PMC3176299.

43. Sankar MM, Singh J, Diana SC, Singh S. Molecular characterization of Mycobacterium tuberculosis isolates from North Indian patients with extrapulmonary tuberculosis. Tuberculosis. 2013;93(1):75–83. doi: 10.1016/j.tube.2012.10.005 23140853.