Rifampicin and isoniazid drug resistance among patients diagnosed with pulmonary tuberculosis in southwestern Uganda

Multidrug-resistant tuberculosis (MDR-TB) has become a major threat to the control of tuberculosis globally. Uganda is among the countries with a relatively high prevalence of tuberculosis despite significant control efforts. In this study, the drug resistance of Mycobacterium tuberculosis to rifampicin (RIF) and isoniazid (INH) was investigated among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda. A total of 283 sputum samples (266 from newly diagnosed and 17 from previously treated patients), collected between May 2018 and April 2019 at four different TB diagnostic centres, were assessed for RIF and INH resistance using high-resolution melt curve analysis. The overall prevalence of monoresistance to INH and RIF was 8.5% and 11% respectively, while the prevalence of MDR-TB was 6.7%. Bivariate analysis showed that patients aged 25 to 44 years were at a higher risk of developing MDR-TB (cOR 0.253). Furthermore, among the newly diagnosed patients, the prevalence of monoresistance to INH, RIF and MDR-TB was 8.6%, 10.2% and 6.4% respectively; while among the previously treated cases, these prevalence rates were 5.9%, 23.5% and 11.8%. These rates are higher than those reported previously indicating a rise in MTB drug resistance and may call for measures used to prevent a further rise in drug resistance. There is also a need to conduct frequent drug resistance surveys, to monitor and curtail the development and spread of drug-resistant TB.

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Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

Journal of Clinical Microbiology ◽

10.1128/jcm.02283-14 ◽

2014 ◽

Vol 53 (1) ◽

pp. 131-135 ◽

Cited By ~ 2

Author(s):

Limei Zhu ◽

Qiao Liu ◽

Leonardo Martinez ◽

Jinyan Shi ◽

Cheng Chen ◽

...

Keyword(s):

Drug Resistance ◽

Diagnostic Value ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Standard Drug ◽

Related Data ◽

Resistant Tuberculosis ◽

Mdr Tb ◽

Previously Treated

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

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Prevalence of Multidrug Resistant Tuberculosis (MDR-TB) in East Africa: a Systematic Review and Meta- Analysis

10.21203/rs.3.rs-731476/v1 ◽

2021 ◽

Author(s):

Kindu Alem

Keyword(s):

Systematic Review ◽

East Africa ◽

Meta Analysis ◽

Multidrug Resistant ◽

Newly Diagnosed ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Pooled Prevalence ◽

Mdr Tb ◽

Previously Treated

Abstract Background: The rate of multidrug resistant tuberculosis is increasing at an alarming rate throughout the world. It is becoming an emerging public health problem in East Africa. Prevalence of MDR-TB among TB positive individuals in the region has not been synthesized. Determining the pooled prevalence of MDR-TB among newly diagnosed and previously treated TB cases in East Africa is the main objective of this review.Methods: In this systematic review and meta-analysis, the researcher searched six electronic databases: Google scholar, PubMed, EMBASE, Scopus, Science direct and Web of Science. Funnel plot symmetry visualization confirmed by Egger’s regression asymmetry test and Begg rank correlation methods was used to assess publication bias. The pooled prevalence estimate was calculated using Der Simonian and Laird’s random Effects model. A total of 16 articles published in East Africa from 2007 and 2019 were included in this study. STATA software (version 14, Texas, USA) was used for analysis. Results: Out of 1025 articles identified citations, a total of 16 articles published in East Africa from 2007 and 2019 were included in this meta-analysis. The pooled prevalence of MDR-TB among newly diagnosed TB cases and previously treated TB patients to be 4% (95%CI=2-5%) and 21% (95%CI: 14-28%), respectively. Living conditions, lifestyles (smoking, alcohol use, and drug abuse), previous medical history, diabetes history and HIV infection risk factors contribute to higher prevalence of MDR-TB in East Africa.Conclusion: An early diagnosis of tuberculosis and rapid detection of drug resistant Mycobacterium tuberculosis is a serious concern to identify patients who are not responding to the standard treatment and to avoid spreading of resistant strains. It is also very essential to strengthen tuberculosis control and improved monitoring of chemotherapy.

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The burden of drug resistance tuberculosis in Ghana; results of the First National Survey

PLoS ONE ◽

10.1371/journal.pone.0252819 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252819

Author(s):

Augustina Angelina Sylverken ◽

Alexander Kwarteng ◽

Sampson Twumasi-Ankrah ◽

Michael Owusu ◽

Rejoice Agyeiwaa Arthur ◽

...

Keyword(s):

Drug Resistance ◽

Previous History ◽

World Health ◽

Multi Drug Resistance ◽

Sputum Smear ◽

Newly Diagnosed ◽

Mdr Tb ◽

Potential Risk Factors ◽

Previously Treated Patients ◽

Previously Treated

Resistance to Tuberculosis drugs has become a major threat to the control of tuberculosis (TB) globally. We conducted the first nation-wide drug resistance survey to investigate the level and pattern of resistance to first-line TB drugs among newly and previously treated sputum smear-positive TB cases. We also evaluated associations between potential risk factors and TB drug resistance. Using the World Health Organization (WHO) guidelines on conducting national TB surveys, we selected study participants from 33 health facilities from across the country, grouped into 29 clusters, and included them into the survey. Between April 2016 and June 2017, a total of 927 patients (859 new and 68 previously treated) were enrolled in the survey. Mycobacterium tuberculosis complex (MTBC) isolates were successfully cultured from 598 (65.5%) patient samples and underwent DST, 550 from newly diagnosed and 48 from previously treated patients. The proportion of patients who showed resistance to any of the TB drugs tested was 25.2% (95% CI; 21.8–28.9). The most frequent resistance was to Streptomycin (STR) (12.3%), followed by Isoniazid (INH) (10.4%), with Rifampicin (RIF), showing the least resistance of 2.4%. Resistance to Isoniazid and Rifampicin (multi-drug resistance) was found in 19 (3.2%; 95% CI: 1.9–4.9) isolates. Prevalence of multidrug resistance was 7 (1.3%; 95% CI: 0.5–2.6) among newly diagnosed and 12 (25.0%; 95% CI: 13.6–39.6) among previously treated patients. At both univariate and multivariate analysis, MDR-TB was positively associated with previous history of TB treatment (OR = 5.09, 95% CI: 1.75–14.75, p = 0.003); (OR = 5.41, 95% CI: 1.69–17.30, p = 0.004). The higher levels of MDR-TB and overall resistance to any TB drug among previously treated patients raises concerns about adherence to treatment. This calls for strengthening existing TB programme measures to ensure a system for adequately testing and monitoring TB drug resistance.

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Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

Journal of International Medical Research ◽

10.1177/0300060520984932 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098493

Author(s):

Jie Zhang ◽

Yixuan Ren ◽

Liping Pan ◽

Junli Yi ◽

Tong Guan ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Drug Testing ◽

Multidrug Resistant ◽

High Rate ◽

Drug Resistant ◽

Surveillance Site ◽

Mdr Tb ◽

Previously Treated Patients ◽

Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

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Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait

Scientific Reports ◽

10.1038/s41598-021-87516-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Noura M. Al-Mutairi ◽

Suhail Ahmad ◽

Eiman Mokaddas

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Mutation Detection ◽

Susceptibility Testing ◽

Multidrug Resistant ◽

Genetic Mutations ◽

Second Line ◽

Injectable Drugs ◽

Mdr Tb ◽

Phenotypic Susceptibility

AbstractMolecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.

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Exploring the Contribution of Mycobacteria Characteristics in Their Interaction with Human Macrophages

Microscopy and Microanalysis ◽

10.1017/s1431927613001906 ◽

2013 ◽

Vol 19 (5) ◽

pp. 1159-1169 ◽

Cited By ~ 3

Author(s):

Carla Silva ◽

Joao Perdigao ◽

Elsa Alverca ◽

António P. Alves de Matos ◽

Patricia A. Carvalho ◽

...

Keyword(s):

Drug Resistance ◽

Cell Envelope ◽

Treatment Strategies ◽

Human Monocyte ◽

Selective Advantage ◽

Multidrug Resistant ◽

Structural Features ◽

Major Health Problem ◽

Transmission Electron ◽

Mdr Tb

AbstractTuberculosis (TB) is a major health problem. The emergence of multidrug resistant (MDR)Mycobacterium tuberculosis(Mtb) isolates confounds treatment strategies. In Portugal, cases of MDR-TB are reported annually with an increased incidence noted in Lisbon. The majority of these MDR-TB cases are due to closely related mycobacteria known collectively as theLisboafamily and Q1 cluster. Genetic determinants linked to drug resistance have been exhaustively studied resulting in the identification of family and cluster specific mutations. Nevertheless, little is known about other factors involved in development of mycobacteria drug resistance. Here, we complement genetic analysis with the study of morphological and structural features of theLisboafamily and Q1 cluster isolates by using scanning and transmission electron microscopy. This analysis allowed the identification of structural differences, such as cell envelope thickness, between Mtb clinical isolates that are correlated with antibiotic resistance. The infection of human monocyte derived macrophages allowed us to document the relative selective advantage of theLisboafamily isolates over other circulating Mtb isolates.

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Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

The Open Conference Proceedings Journal ◽

10.2174/2210289201708010033 ◽

2017 ◽

Vol 8 (1) ◽

pp. 33-43 ◽

Cited By ~ 2

Author(s):

Aleksandr I. Ilin ◽

Murat E. Kulmanov ◽

Ilya S. Korotetskiy ◽

Marina V. Lankina ◽

Gulshara K. Akhmetova ◽

...

Keyword(s):

Clinical Trial ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Genetic Heterogeneity ◽

Multidrug Resistant ◽

Resistance Mutations ◽

General Increase ◽

Drug Induced ◽

Mdr Tb ◽

Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

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Biological microchips for detection of multiple drug resistant M. tuberculosis strains isolated in Kyrgyz Republic

Russian Pulmonology ◽

10.18093/0869-0189-2008-0-3-64-66 ◽

2008 ◽

pp. 64-66

Author(s):

J. T. Isakova ◽

Z. K. Goncharova ◽

A. A. Aldashev

Keyword(s):

Drug Resistance ◽

Pulmonary Tuberculosis ◽

Gene Mutations ◽

Rpob Gene ◽

Multiple Drug ◽

Drug Resistant ◽

Kyrgyz Republic ◽

Newly Diagnosed ◽

Single Drug ◽

Multiple Drug Resistant

The aim of the study was to estimate spread of primary and secondary multiple drug resistant Mycobacterium tuberculosis (MBT) and to characterize rpoB, katG, inhA, and ahpC gene mutations of rifampicin (RIF) and isoniazid (INH) resistant MBT strains isolated from tuberculosis patients in Kyrgyz. We obtained 493 specimens from patients with pulmonary tuberculosis which were diagnosed based on clinical, X-ray, and bacteriological examination. Among them, newly diagnosed pulmonary tuberculosis was in 445 patients (90.2 %), and 48 of the patients (9.8 %) have already been treated for tuberculosis. Mutations of rpoB, KatG, inhA, and ahpC genes associated with RIF and INH resistance were detected by biological chip test. Sensitive MBT strains were detected in 47 % and resistant strains were in 53 % of the newly diagnosed patients. Single-drug resistance to RIF only was detected in 3 % of cases; resistance to INH was found in 20 %, resistance to both the drugs was detected in 30 % of the patients. In pre-treated patients single-drug resistance to RIF was defined in 4 % of cases, resistance to INH was in 8 %, resistance to both the drugs was estimated in 75 % of the patients. Therefore, we suppose that there is a high prevalence of multi-drug resistant MBT in Kyrgyz Republic: 30 % among newly diagnosed patients and 75 % among pre-treated patients. The main cause of RIF-resistance of MBT is Ser531→Leu mutation of rpoB gene, and the main cause of INHresistance is Ser315→Thr mutation of katG gene.

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Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa148 ◽

2020 ◽

Author(s):

Janisara Rudeeaneksin ◽

Benjawan Phetsuksiri ◽

Chie Nakajima ◽

Supranee Bunchoo ◽

Krairerk Suthum ◽

...

Keyword(s):

Drug Resistance ◽

Variable Number Tandem Repeat ◽

Multidrug Resistant ◽

Variable Number ◽

Drug Resistant ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Extensively Drug Resistant ◽

Mdr Tb ◽

Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

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