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 AiM  Vol.7 No.3 , March 2017
Mycobacteria Interspersed Repetitive Units-Variable Number of Tandem Repeat, Spoligotyping and Drug Resistance of Isolates from Pulmonary Tuberculosois Patients in Kenya
Abstract: Background: Molecular typing allows a rapid and precise species differentiation and is essential in investigating the spread of specific genotypes and any relationship with drug resistance. Methodology: To compare the discrimination power of 24-loci Mycobacteria interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) to spoligotyping in determining the circulating genotypes of Mycobacterium tuberculosis in isolates from pulmonary tuberculosis patients in Kenya, a total of 204 isolates were typed. Results: Spoligotyping identified 22 spoligo lineages; while 36(17.6%) isolates were not determined. MIRU-VNTR typing identified 12 genotypes; Kenya H37_Rv_ like, S-like that had never been reported before and which were not identified by spoligotyping were identified. Others were Uganda I and II, LAM, Beijing, TUR, EAI, Delhi/C, S and Haarlem. Only 8 (3.9%) were not defined by MIRU-VNTR. Delhi/CAS, EAI, S, S-like, LAM and Beijing had strains that showed resistance to all the five drugs tested. Two strains of EAI and 2 of S genotypes were resistant to all the five drugs tested. Beijing genotype commonly associated with drug resistance was found to be third in drug resistance (14.7%) after Delhi/CAS (28.9%) and LAM (17.6%) with the highest resistance towards isoniazid and pyrazinamide (3.9% each). MIRU-VNTR typing was more discriminative than spoligotyping; identifying 10 unique H37_Rv-like isolates designated KeniaH37_Rv_like genotype and 14 S-like genotype. Conclusion: MIRU-VNTR typing has not been reported in any other study in Kenya and its higher discrimination can help identify genotypes that cannot be determined by spoligotyping. Association of Beijing genotype drug resistance particularly isoniazid should be of concern since it may result in multidrug resistance in the patients.
Cite this paper: Ndungu, P. , Kariuki, S. , Revathi, G. , Ng’ang’a, Z. and Niemann, S. (2017) Mycobacteria Interspersed Repetitive Units-Variable Number of Tandem Repeat, Spoligotyping and Drug Resistance of Isolates from Pulmonary Tuberculosois Patients in Kenya. Advances in Microbiology, 7, 205-216. doi: 10.4236/aim.2017.73017.
References

[1]   Wayne, L.G., Brenner, D.J., Colwell, R.R., Grimont, P.A.D., Kandler, O., Krichevsky, M.I., Moore, L.H., Moore, W.E., Murray, R.G., Stackebrandt, E., Starr, M. P. and Truper, H.G. (1987) Report of the Ad Hoc Committee on Reconciliation of Approaches to Bacterial Systematics. International Journal of Systematic and Evolutionary Microbiology, 37, 463-464.
https://doi.org/10.1099/00207713-37-4-463

[2]   Van Embden, J.D., Cave, M.D., Crawford, J.T., Dale, J.W., Eisenach, K.D., Gicquel, B., Hermans, P., Martin, C., McAdam, R. and Shinnick, T.M. (1993) Strain Identification of Mycobacterium tuberculosis by DNA Fingerprinting: Recommendations for Standardized Methodology. Journal of Clinical Microbiology, 31, 406-409.

[3]   Kamberbeek, J., Schouls, L., Kolk, A., van Agterveld, M., van Sooligen, D., Kuijper, S., Bunchoten, A., Molhuizen, H. and Shaw, R. (1997) Simultaneous Detection and Strain Differentiation of Mycobacterium tuberculosis for Diagnosis and Epidemiology. Journal of Clinical Microbiology, 35, 907-914.

[4]   Filliol, I., Driscoll, J.R., Van Soolingen, D., Kreiswirth, B.N., Kremer, K., et al. (2002) Snapshot of Moving and Expanding Clones of Mycobacterium tuberculosis and Their Global Distribution Assessed by Spoligotyping in an International Study. Journal of Clinical Microbiology, 41, 1963-1970. https://doi.org/10.1128/JCM.41.5.1963-1970.2003

[5]   Groenen, P.M., Bunschoten, E.A., van Soolingen, D. and van Errtbden, J.D. (1993) Nature of DNA Polymorphism in Direct Repeat Cluster of Mycobacterium tuberculosis: Application for Strain Differentiation by a Novel Typing Method. Molecular Microbiology, 10, 1057-1065.
https://doi.org/10.1111/j.1365-2958.1993.tb00976.x

[6]   Kremer, K., van Soolingen, D., Forthingham, R., Haas, W.H., Hermans, P.W., Martin, C., Pallittapongarnpim, P., Plikaytis, B.B., Riley, L.W., Yakrus, M.A., Musser, J.M. and van Embden, J.D (1999) Comparison of Methods Based on Different Molecular Epidemiological Makers for Typing of Mycobacterium tuberculosis Complex Strains: Interlaboratory Study of Discriminatory Power and Reproducibility. Journal of Clinical Microbiology, 37, 2607-2618.

[7]   Jafarian, M., Aghali-Merza, M., Farnia, P., Ahmadi, M., Mesjedi, M.R. and Velayati, A.A. (2010) Synchronous Comparison of Mycobacterium tuberculosis Epidemiology Strains by MIRU-VNTR and MIRU-VNTR and Spoligotyping Technique. Avicenna Journal of Medical Biotechnology, 2, 145-148.

[8]   Supply, P., Mazars, E., Lesjean, S., Vincent, V., Gicquel, B. and Locht, C. (2000) Variable Human Minisatellite-Like Regions in the Mycobacterium tuberculosis Genome. Molecular Microbiology, 36, 762-771. https://doi.org/10.1046/j.1365-2958.2000.01905.x

[9]   Supply, P., Lesjean, E., Savine, K., Kremer, D., van Soolingen, J. and Locht, C. (2001) Automated High Through-Put Genotyping for Study of Global Epidemiology of Mycobacterium tuberculosis Based on Mycobacterial Interspersed Repetitive Units. Journal of Clinical Microbiology, 39, 3563-3571. https://doi.org/10.1128/JCM.39.10.3563-3571.2001

[10]   Cowan, L., Diem, L., Monson, T., Wand, P., Temporado, D., Oemig, T.V. and Crawford, J.T. (2005) Evaluation of a Two-Step Approach for Large Scale, Prospective Genotyping of Mycobacterium tuberculosis Isolates in the United States. Journal of Clinical Microbiology, 43, 688-695. https://doi.org/10.1128/JCM.43.2.688-695.2005

[11]   Kremer, K., Arnold, C., Cataldi, A., Gutierrez, M.C., Haas, W.H., Panaiotor, S., Skuce, R.A., Supply, P., van der Zanden, A.G. and van Soolingen, D. (2005) Discriminatory Power and Reproducibility of Novel DNA Typing Methods for Mycobacterium tuberculosis Isolates. Journal of Clinical Microbiology, 41, 2683-2685.

[12]   Sola, C., Filliol, I., Legrand, E., Lesjean, S., Locht, C., Supply, P. and Rastogi, N. (2003) Genotyping of Mycobacterium tuberculosis Complex Using MIRUs: Association with VNTR and Spoligotyping for Molecular Epidemiology and Evolutionary Genetics. Infection, Genetics and Evolution, 3, 125-133.

[13]   Supply, P., Warren, R.M., Banuls, A.L., Lesjean, S., van der Spuy, G.D., et al. (2003) Linkage Disequilibrium between Minisatellite Loci Supports Clonal Evolution of Mycobacterium tuberculosis in a High Tuberculosis Incidence Area. Molecular Microbiology, 47, 529-538.
https://doi.org/10.1046/j.1365-2958.2003.03315.x

[14]   Kanduma, E., McHugh, T.D. and Gillespie, S.H. (2003) Molecular Methods for Mycobacterium tuberculosis Strain Typing: A User’s Guideline. Journal of Applied Microbiology, 94, 781-791.
https://doi.org/10.1046/j.1365-2672.2003.01918.x

[15]   Mazars, E., Lesjean, S., Banuls, A.L., Gilbert, M., Vincent, V., Gicquel, B., Tibayrenc, M., Locht, C. and Supply, D. (2001) High Resolution Minisatellite-Based Typing as a Portable Approach to Global Analysis of Mycobacterium tuberculosis Molecular Epidemiology. Proceedings of the National Academy of Sciences of the United States of America, 98, 1901-1906. https://doi.org/10.1073/pnas.98.4.1901

[16]   Kam, K.M., Yip, C.W., Tse, L.W., Wong, K.L., Lam, T.K., Kremer, K., Au, B.K. and van Soolingen, D. (2005) Utility of Mycobacterium Interspersed Repetitive Unit Typing for Differentiating Multi-Drug Resistant Mycobacterium tuberculosis Isolates of the Beijing Family. Journal of Clinical Microbiology, 43, 306-313. https://doi.org/10.1128/JCM.43.1.306-313.2005

[17]   Weniger, T., Krawczyk, J., Supply, P., Niemann, S. and Harmsen, D. (2010) MIRU-VNTRplus: A Web Tool for Polyphasic Genotyping of Mycobacterium tuberculosis Complex Bacteria. Nucleic Acids Research, 38, W326-W331. https://doi.org/10.1093/nar/gkq351

[18]   Allix-Beguec, C., Fauville-Dufaux, M. and Supply, P. (2008) Three-Year Population-Based Evaluation of Standardized Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat Typing of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 46, 1398-1406. https://doi.org/10.1128/JCM.02089-07

[19]   Supply, P., Allix, C., Lesjean, S., Cardoso-Oelemann, M., Rusch-Gerdes, S., Willey, DE., Savine, E., de Haas, P., van Deutekom, H., Roring, S., Bifani, P., Kurepina, N., Kreiswirth, B., Sola, C., Rastogi, N., Vatin, V., Gutierrez, M.C., Fauville, M., Niemann, S., Skuce, R., Kremer, K., Locht, C. and van Soolingen, D. (2006) Proposal for Standardization of Optimized Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeat Typing of Mycobacterium tuberculosis. Journal of Clinical Microbiology, 44, 4498-4510.
https://doi.org/10.1128/JCM.01392-06

[20]   Murray, P.R., Baron, E.J., Jorgensen, J.H., Landry, M.L. and Pfaller, M.A. (2007) Manual of Clinical Microbiology. 9th Edition, Vol. 1, American Society for Microbiology, 563.

[21]   Kremer, K., Bunschoten, A., Schouls, L., van Soolingen, D. and van Embden, J. (1997) A PCR-Based Method to Simultaneously Detect and Type Mycobacterium tuberculosis Complex Bacteria. Research Laboratory for Infectious Diseases, National Institute of Public Health and Environment, Bilthoven.

[22]   Brudey, K., Driscoll, J.R., Rigouti, L., Prodinger, W.M., Gori, A., Attlojog, S.A., Allix, C., Aristimuno, L., Arora, J., et al. (2006) Mycobacterium tuberculosis Complex Genetic Diversity: Mining the Fourth International Database (SpolDB4) for Classification, Population Genetics and Epidemiology. BMC Microbiology, 6, 23. https://doi.org/10.1186/1471-2180-6-23

[23]   Kibiki, G.S., Mulder, B., Dolmans, W.M.V., de Beer, J.L., Boeree, M., Sam, N., van Soolingen, D., Sola, C. and van der Zanden, A.G.M. (2007) M. tuberculosis Genetic Diversity and Drug Susceptibility Pattern in HIV-Infected and Non-HIV-Infected Patients in Northern Tanzania. BMC Microbiology, 7, 51. https://doi.org/10.1186/1471-2180-7-51

[24]   Ogaro, T.D., Githui, W., Kikuvi, G., Okari, J., Asiko, V., Wangui, E., Jordan, A.M. and Van Helden, P.D. (2012) Diversity of Mycobacterium tuberculosis Strains in Nairobi Kenya. African Journal of Health Sciences, 20, 82-90.

[25]   Kisa, O., Tarhar, G., Gunal, S., Albay, A., Durmaz, R., Saribes, Z., Zozo, T., Alp, A., Ceyham, I., Tombak, A. and Rastogi, N. (2012) Distribution of Spoligotyping Defined Genotypic Lineages among Drug-Resistant Mycobacterium tuberculosis Complex Clinical Isolates in Ankara Turkey. PLoS ONE, 7, e30331. https://doi.org/10.1371/journal.pone.0030331

[26]   Varma-Basil, M., Kumar, S. Arora, J., Anqrup, A., Zozio, T., Banavaliker, J.N., Sinqh, U.B., Rastogi, N. and Bose, M. (2011) Comparison of Spoligotyping, Mycobacterial Interspersed Repetitive Units Typing and IS6110-RFLP in a Study of Genotypic Diversity of Mycobacterium tuberculosis in Delhi North India. Memórias do Instituto Oswaldo Cruz, 106, 524-535.
https://doi.org/10.1590/S0074-02762011000500002

[27]   Guernier, V., Sola, C., Brudey, K., Guegan, J. and Rastogi, N. (2008) Use of Cluster-Graph from Spoligotyping Data to Study Genotype Similarities and Comparison of Three Indices to Quantify Recent Tuberculosis Transmission among Culture Positive Cases in French Guiana during a Eight Year Period. BMC Infectious Diseases, 8, 46.
https://doi.org/10.1186/1471-2334-8-46

[28]   Githui, W.A., Jordaan, A.M., Juma, E.S., Kinyanjui, P., Karimi, F.G., Kimwomi, J., Meme, H., Mumbi, P., Steicher, E.M., Warren, R., Van Helden, P.D. and Victor, T.C. (2004) Identification of MDR-TB Beijing/W and Other Mycobacterium tuberculosis Genotypes in Nairobi Kenya. International Journal of Tuberculosis and Lung Disease, 8, 352-360.

[29]   Anderson, J., Jarlsberg, L.G., Grindsdale, J., Osmond, D., Kawamura, M., Hopewell, P.C. and Kato-Maeda, M. (2013) Sublineage of Lineage 4 (Euro-American) Mycobacterium tuberculosis Differs in Genotypic Clustering. The International Journal of Tuberculosis and Lung Disease, 17, 885-891. https://doi.org/10.5588/ijtld.12.0960

[30]   Bhanu, N.V., van Soolingen, D, van Embden, J.D., Dar, L., Pandey, R.M. and Seth, P. (2002) Predominance of a Novel Mycobacterium tuberculosis Genotype in Delhi Region of India. Tuberculosis Home, 82, 105-112. https://doi.org/10.1054/tube.2002.0332

[31]   Singh, U.B., Suresh, N., Bhanu, N.V., Arora, J., Pant, H., Sinha, S., Aggrwal, R.C., Singh, S., Pande, J.N., Sola, C., Rastogi, N. and Seth, P. (2004) Predominant Tuberculosis Spoligotypes Delhi, India. Emerging Infectious Diseases, 10, 1138-1142.
https://doi.org/10.3201/eid1006.030575

[32]   Singh, M., Mynak, M.L., Kumar, L., Matthew, J.L. and Jindal, S.K. (2005) Prevalence and Risk Factors for Transmission of Infection among Children in Household Contact with Adult Having Pulmonary Tuberculosis. Archives of Disease in Childhood, 90, 624-628.
https://doi.org/10.1136/adc.2003.044255

[33]   European concerted Action on New Generation Genetic Markers and Techniques for Epidemiology and Control of Tuberculosis (2006) Beijing Genotype Mycobacterium tuberculosis and Drug Resistance. Emerging Infectious Diseases, 12, 736-743.

[34]   Yang, C., Luo, T., Sun, G., Qiao, K., Sun, G., DeRiemer, K., Mei, J. and Gao, Q. (2012) Mycobacterium tuberculosis Beijing Strains Favor Transmission but Not Drug Resistance in China. Clinical Infectious Diseases, 5, 1179-1187. https://doi.org/10.1093/cid/cis670

[35]   Anh, D.D., Bordorff, M.W., Van, L.N., Lan, N.T., Van Gorkom, T., Kremer, K. and Van Soolingen, D. (2000) Mycobacterium tuberculosis Beijing Genotype Emerging in Vietnam. Emerging Infectious Diseases, 6, 302-305. https://doi.org/10.3201/eid0603.000312

 
 
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