Molecular Characterization and RIF Resistance Mutation Pattern in Multi Drug Resistance Isolates Using Xpert MTB/RIF Assay in Clinical Isolates from Quetta, Pakistan
DOI:
https://doi.org/10.5281/zenodo.16608758Keywords:
Multidrug-resistant tuberculosis , Rifampicin resistance determining region, Xpert MTB/RIFAbstract
Multidrug-resistant tuberculosis (MDR-TB) is currently one of the serious global challenges. With the advancement in the diagnostic facilities against tuberculosis and the advent of Xpert assay, the diagnosis of MDR-TB has become easier and more reliable. A total of 6353 specimens received at Fatima Jinnah Chest Hospital, Quetta, were screened through fluorescent microscopy and GeneXpert assay from 2016 to 2018. The data collected were analyzed using SPSS. Out of 6353 specimens, 1297 mycobacterium tuberculosis (MTB) positive cases were detected by Xpert assay, with 184 demonstrating rif resistance, mutations in the 81bp RRD region. The frequency of different probes was as follows: probe E 98/184 (53%), D 23/184 (12.5%), B 15/184 (8.1%), C 5/184 (2.7%), A 3/184 (1.6%), double probe mutation 5/184 (2.7%), D&E 3/184 (1.6%), and C&D 2/184 (1%) and all 5-probe mutation 35/184 (19%). A statistically significant association was found between probe type and gender and treatment history, while no significant association was found between probe type and age group of patients. MDR-TB prevalence was 184/1297 (14.18%) with dominance of Probe E (53.26%) in the population studied. This study explores the increasing pattern of MDR-TB in the area. Effective measures should be adopted to curtail the disease in the area.
References
Ahmad, N., Javaid, A., Sulaiman, S. A., Ming, L. C., Ahmad, I., & Khan, A. H. (2016). Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. The Brazilian Journal of Infectious Diseases, 20(1), 41-47. https://doi.org/10.1016/j.bjid.2015.09.011
Boehme, C. C., Nabeta, P., Hillemann, D., Nicol, M. P., Shenai, S., Krapp, F., Allen, J., Tahirli, R., Blakemore, R., Rustomjee, R., Milovic, A., Jones, M., O'Brien, S. M., Persing, D. H., Ruesch-Gerdes, S., Gotuzzo, E., Rodrigues, C., Alland, D., & Perkins, M. D. (2010). Rapid molecular detection of tuberculosis and rifampin resistance. The New England Journal of Medicine, 363(11), 1005–1015. https://doi.org/10.1056/NEJMoa0907847
Ejaz, M., Siddiqui, A. R., Rafiq, Y., Malik, F., Channa, A., Mangi, R., Habib, F., & Hasan, R. (2010). Prevalence of multi-drug resistant tuberculosis in Karachi, Pakistan: Identification of at risk groups. Transactions of the Royal Society of Tropical Medicine and Hygiene, 104(8), 511-517. https://doi.org/10.1016/j.trstmh.2010.03.005
Heep, M., Brandstätter, B., Rieger, U., Lehn, N., Richter, E., Rüsch-Gerdes, S., & Niemann, S. (2001). Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. Journal of Clinical Microbiology, 39(1), 107-110. https://doi.org/10.1128/JCM.39.1.107-110.2001
Ioerger, T. R., Koo, S., No, E. G., Chen, X., Larsen, M. H., Jacobs Jr, W. R., Pillay, M., Sturm, A. W. & Sacchettini, J. C. (2009). Genome analysis of multi-and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa. PLoS ONE, 4(11), e7778. https://doi.org/10.1371/journal.pone.0007778
Javaid, A., Hasan, R., Zafar, A., Ghafoor, A., Pathan, A. J., Rab, A., ... & Shaheen, Z. (2008). Prevalence of primary multidrug resistance to anti-tuberculosis drugs in Pakistan. The International Journal of Tuberculosis and Lung Disease, 12(3), 326-331.
Khan, S. N., Niemann, S., Gulfraz, M., Qayyum, M., Siddiqi, S., Mirza, Z. S., Tahsin, S., Ebrahimi-Rad, M., & Khanum, A. (2013). Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in Punjab, Pakistan. Pakistan Journal of Zoology, 45(1), 93–100.
Liu, Q., Zhu, L., Shao, Y., Song, H., Li, G., Zhou, Y., Shi, J., Zhong, C., Chen, C., & Wei, L. (2013). Rates and risk factors for drug resistance tuberculosis in Northeastern China. BMC Public Health, 13(1), 1171. https://doi.org/10.1186/1471-2458-13-1171
Luiz, R. D. S. S., Suffys, P., Barroso, E. C., Kerr, L. R. F. S., Duarte, C. R., Freitas, M. V. C., Mota, R. M. S., & Frota, C. C. (2013). Genotyping and drug resistance patterns of Mycobacterium tuberculosis strains observed in a tuberculosis high-burden municipality in Northeast, Brazil. The Brazilian Journal of Infectious Diseases, 17(3), 338-345. https://doi.org/10.1016/j.bjid.2012.10.019
Mboowa, G., Namaganda, C., & Ssengooba, W. (2014). Rifampicin resistance mutations in the 81 bp RRDR of rpoB gene in Mycobacterium tuberculosis clinical isolates using Xpert® MTB/RIF in Kampala, Uganda: A retrospective study. BMC Infectious Diseases, 14(1), 481. https://doi.org/10.1186/1471-2334-14-481
Metcalfe, J. Z., Makumbirofa, S., Makamure, B., Sandy, C., Bara, W., Mason, P., & Hopewell, P. C. (2016). Xpert® MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe. The International Journal of Tuberculosis and Lung Disease, 20(7), 882-889. https://doi.org/10.5588/ijtld.15.0696
Ong, D. C., Yam, W. C., Siu, G. K., & Lee, A. S. (2010). Rapid detection of rifampicin-and isoniazid-resistant Mycobacterium tuberculosis by high-resolution melting analysis. Journal of Clinical Microbiology, 48(4), 1047-1054. https://doi.org/10.1128/jcm.02036-09
Ramaswamy, S., & Musser, J. M. (1998). Molecular genetic basis of antimicrobial agent resistance inMycobacterium tuberculosis: 1998 update. Tubercle and Lung disease, 79(1), 3-29. https://doi.org/10.1054/tuld.1998.0002
Reddy, R., & Alvarez-Uria, G. (2017). Molecular epidemiology of rifampicin resistance in Mycobacterium tuberculosis using the GeneXpert MTB/RIF assay from a rural setting in India. Journal of Pathogens, 2017, 6738095. https://doi.org/10.1155/2017/6738095
Scorpio, A., & Zhang, Y. (1996). Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nature medicine, 2(6), 662-667. https://doi.org/10.1038/nm0696-662
Siddique, G., Shafee, M., Abbas, F., Naeem, M., Raziq, A., Ahmad, S., & Babar, K. M. (2019). Mycobacterium tuberculosis; frequency of rifampin resistance mutations in 81-bp rrdr of rpob gene in mycobacterium tuberculosis isolates in Quetta, Pakistan. The Professional Medical Journal, 26(05), 780-786. https://doi.org/10.29309/TPMJ/2019.26.05.3477
Telenti, A., Philipp, W. J., Sreevatsan, S., Bernasconi, C., Stockbauer, K. E., Wieles, B., Musser, J. M. & Jacobs Jr, W. R. (1997). The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nature Medicine, 3(5), 567-570. https://doi.org/10.1038/nm0597-567
Ullah, I., Javaid, A., Tahir, Z., Ullah, O., Shah, A. A., Hasan, F., & Ayub, N. (2016). Pattern of drug resistance and risk factors associated with development of drug resistant Mycobacterium tuberculosis in Pakistan. PLoS ONE, 11(1), e0147529. https://doi.org/10.1371/journal.pone.0147529
Ullah, I., Shah, A. A., Basit, A., Ali, M., Khan, A., Ullah, U., Ihtesham, M., Mehreen, S., Mughal, A., & Javaid, A. (2016). Rifampicin resistance mutations in the 81 bp RRDR of rpo B gene in Mycobacterium tuberculosis clinical isolates using Xpert MTB/RIF in Khyber Pakhtunkhwa, Pakistan: A retrospective study. BMC Infectious Diseases, 16(1), 413. https://doi.org/10.1186/s12879-016-1745-2
World Health Organization -WHO- (2018). Global tuberculosis report 2018. Geneva, Switzerland: World Health Organization, WHO Press.
Yue, J., Shi, W., Xie, J., Li, Y., Zeng, E., & Wang, H. (2003). Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis isolates from China. Journal of Clinical Microbiology, 41(5), 2209-2212. https://doi.org/10.1128/jcm.41.5.2209-2212.2003
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Optimum Science Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
