Compensatory mutations of rifampicin resistance facilitate transmission of multidrug-resistant Mycobacterium tuberculosis in China

Author(s):  
Wei-Wei Jiao
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anwar Sheed Khan ◽  
Jody E. Phelan ◽  
Muhammad Tahir Khan ◽  
Sajid Ali ◽  
Muhammad Qasim ◽  
...  

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan.


2016 ◽  
Vol 5 (2) ◽  
pp. 226-230 ◽  
Author(s):  
Justice K. Boakye-Appiah ◽  
Alexis R. Steinmetz ◽  
Peter Pupulampu ◽  
Stephen Ofori-Yirenkyi ◽  
Ishmael Tetteh ◽  
...  

2020 ◽  
Author(s):  
Getachew Kahsu Abay ◽  
Bahlibi Hailay

Abstract Background: Tuberculosis is an infectious disease usually caused by Mycobacterium tuberculosis bacteria. The global emergence of mono- or multidrug-resistant tuberculosis and extensively drug-resistant forms of tuberculosis poses a considerable challenge to tuberculosis control programs. There has been no reliable and organized data on trends and drug resistance of Mycobacterium tuberculosis in the study area. Therefore, this study aimed to determine the trends of Mycobacterium tuberculosis and Rifampicin resistance in the Adigrat General Hospital, eastern zone, Tigray, Northern Ethiopia.Methods: A hospital-based retrospective cross-sectional study was conducted at Adigrat General Hospital from January 2015 to 2018. Data were collected retrospectively from the GenexpertTM TB registration books using a data extraction format. Data was entered into Epi-Info 3.1 and subsequently exported and analyzed using SPSS Version 20. The results were summarized using descriptive statistics, tables, and figures. P values < 0.05 were considered statistically significant.Result: A total of 5,944 Mycobacterium tuberculosis presumptive patients were included in the study. The majority of the study participants were male (58.1%) with participants’ median age of 40.0 (IQR 57, 26) years, the majority were 30-44 years. The overall positive cases of Mycobacterium tuberculosis was 24.3% (1446) with a total of 132 (9.1%) found to be resistant to rifampicin. Within the total Rifampicin resistant sub-group, 129/132 (97.7 %) were newly identified cases and the rest were previously treated, tuberculosis patients. Age, the reason for diagnosis, site of presumptive tuberculosis, and/or being HIV infected showed significant association with our dependent variable; however, only age and being HIV infected were associated with rifampicin resistance.Conclusion: In our study, the overall trends of Mycobacterium tuberculosis and rifampicin resistance were found to be high and gradually increasing. HIV co-infected and previously treated patients were more likely to develop rifampicin resistance. Therefore, maximizing early detection of drug-resistant Mycobacterium tuberculosis and strengthening tuberculosis infection control activities are recommended to reduce the burden of this contagious and potentially deadly disease.


2020 ◽  
Author(s):  
Getachew Kahsu Abay ◽  
Bahlibi Hailay

Abstract Background: Tuberculosis is an infectious disease usually caused by Mycobacterium tuberculosis bacteria. The global emergence of mono- or multidrug-resistant tuberculosis and extensively drug-resistant forms of tuberculosis poses a considerable challenge to tuberculosis control programs. There has been no reliable and organized data on trends and drug Resistance of Mycobacterium tuberculosis in the study area. Therefore, this study aimed to determine the trends of Mycobacterium tuberculosis and rifampicin Resistance in the Adigrat General Hospital, eastern zone of Tigrai, North Ethiopia.Methods: A hospital-based retrospective cross-sectional study was conducted at Adigrat General Hospital from January 2015 to 2018. Data were collected retrospectively from the GenexpertTM TB registration book using a data extraction format. Data was entered into Epi-Info 3.1 and subsequently exported and analyzed using SPSS Version 20. The results were summarized using descriptive statistics, tables, and figures. Bivariate and multi-variant regression analysis were employed to measure the association between dependent and independent variables. P values < 0.05 were considered statistically significant.Result: A total of 5,944 Mycobacterium tuberculosis presumptive patients were included in the study. The majority of the study participants were male (58.1%) with participants’ median age of 40.0 (IQR 26-57) years, the majority were 30-44 years. The overall positive cases of Mycobacterium tuberculosis was 24.3% (1446) with a total of 132 (9.1%) found to be resistant to Rifampicin. Within the total Rifampicin resistant sub-group, 129/1385 (9.3 %) were newly identified cases and the rest were previously treated, tuberculosis patients. Age, the reason for diagnosis, site of presumptive tuberculosis, and/or being HIV infected showed significant association with our dependent variable; however, only age and being HIV infected were associated with Rifampicin Resistance.Conclusion: In our study, the overall trends of Mycobacterium tuberculosis and rifampicin Resistance were found to be constant. HIV co-infected and previously treated patients were more likely to develop Rifampicin Resistance. Therefore, maximizing early detection of drug-resistant Mycobacterium tuberculosis and strengthening tuberculosis infection control activities are recommended to reduce the burden of this contagious and potentially deadly disease.


2020 ◽  
Author(s):  
Getachew Abay Kahsu ◽  
Bahlibi Hailay

Abstract Background Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. The emergence of Mono or multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis (XDR-TB), poses a considerable challenge to Mycobacterium tuberculosis control programs in the worldwide; however, there has been no reliable and organized data on trends and prevalence drug resistance of Mycobacterium tuberculosis in study area; Therefore, aim of this study to determine the trends of Mycobacterium tuberculosis and prevalence of Rifampicin resistance in eastern zone, Tigray, Northern Ethiopia. Methods Hospital based retrospective cross-sectional study was conducted at Adigrat General Hospital from June 01 to August 30, 2019.Data was collected retrospectively from the registration books using data extraction format commence January 01, 2015, December 30, 2018. Data was entered into Epi-Info 3.1 and exported and analyzed using SPSS Version 20. The results were summarized using descriptive statistics, tables, and figures. P values < 0.05 would be considered statistically significant. Result A total of 5,944 Mycobacterium tuberculosis presumptive patients were included in the study. The majority of the study participants were male (58.1%). The median age of the participants was 40.0 (IQR 57, 26) years, the majority age-group was 30-44 years. The overall prevalence of Mycobacterium tuberculosis was 1446 (24.3%). Of the total confirmed cases, 132 (9.1%) were resistant to rifampicin. From total Rifampicin resistant 129 (97.7%) new cases and the rest were previously treated tuberculosis patients. Age, reason for diagnosis, site of presumptive tuberculosis, being HIV infected was found a significant association with our dependent variable; however, only Age and being HIV infected associated with rifampicin resistance. Conclusion In our study, the overall trends of Mycobacterium tuberculosis and prevalence of rifampicin resistance were found high and increased; therefore, maximizing early detection of drug-resistant Mycobacterium tuberculosis and strengthening TB infection control activities and proper implementation of directly observed treatment are recommended reducing the burden of this contagious disease.


2014 ◽  
Vol 3 (3) ◽  
pp. 173-177 ◽  
Author(s):  
Obaidullah Qazi ◽  
Hazir Rahman ◽  
Zarfishan Tahir ◽  
Muhammad Qasim ◽  
Sajid Khan ◽  
...  

2021 ◽  
Author(s):  
Qi Jiang ◽  
Hai-can Liu ◽  
Qing-yun Liu ◽  
Jody E. Phelan ◽  
Li Shi ◽  
...  

ABSTRACTObjectiveTibet has the highest prevalence of both tuberculosis disease and multidrug-resistant tuberculosis (MDR-TB) in China. The circulated Mycobacterium tuberculosis strains from Tibet were sequenced to investigate the underlying drivers for the high burden of MDR-TB.MethodsUsing whole-genome sequencing data of 576 M. tuberculosis strains isolated from consecutive patients in Tibet, we mapped resistance-conferring mutations onto phylogenetic trees to determine their evolution and spread. The impact of drug resistance on bacterial population growth was assessed with a Bayesian (Skyline Plot) analysis. Multivariable logistic regression was used to identify risk factors for the development of rifampicin resistance.ResultsOf the 576 isolates, 284 (49.3%), 280 (48.6%), and 236 (41.0%) were, respectively, genetically resistant to isoniazid, rifampicin, or both (MDR-TB). Among the isoniazid- and rifampicin-resistant strains, the proportions in phylogenetically-inferred clusters were 77.8% (221/284) and 62.1% (174/280), respectively. Nearly half (47.2%, 134/284) of the isoniazid-resistant strains were in six major clades, which contained between 8 and 58 strains with katG S315T, katG S315N, or fabG1 promoter −15 C>T resistance mutations. These major clades exponentially expanded after emerging with isoniazid resistance and stabilized before evolving into MDR-TB twenty years later. Isoniazid-resistant isolates showed an increased risk of accumulating rifampicin resistance compared to isoniazid-susceptible strains, with an adjusted odds ratio of 3.81 (95% confidence interval 2.47-5.95).ConclusionHistorical expansion of isoniazid-resistant strains and their increased likelihood of acquiring rifampicin resistance both contributed to the high burden of MDR-TB in Tibet, highlighting the need to detect INH-resistant strains promptly and to control their transmission.


Antibiotics ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 18 ◽  
Author(s):  
Diana Machado ◽  
João Perdigão ◽  
Isabel Portugal ◽  
Marco Pieroni ◽  
Pedro Silva ◽  
...  

2013 ◽  
Vol 21 (3) ◽  
Author(s):  
Cătălina Luncă ◽  
Olivia S. Dorneanu ◽  
Daniela Diculencu ◽  
Teodora Vremeră ◽  
Aida C. Bădescu ◽  
...  

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