Prevalence Of Drug-resistant Tuberculosis Research Articles

Prevalence of Drug-Resistant Tuberculosis in HIV-Positive and Diabetic Patients in Sinaloa, Mexico: A Retrospective Cross-Sectional Study.

Tuberculosis (TB) is a disease caused by the bacillus Mycobacterium tuberculosis (MTB). Human immunodeficiency virus (HIV) infection and type 2 diabetes mellitus (T2DM) are among the main risk factors for the development of TB and increase the risk of drug-resistant TB developing (DR-TB). The aim of this study was to estimate the prevalence of DR-TB in patients with HIV or T2DM in Sinaloa, Mexico. This was an observational and cross-sectional study. The analysis was conducted using the clinical data of patients registered on the National Epidemiological Surveillance System for TB (SINAVE/PUI-TB) platform with a presumed diagnosis of TB during 2019 to 2021 in Sinaloa, Mexico. The prevalence of DR-TB was estimated in HIV and T2DM patients, as well as the odds ratios for their sociodemographic variables, using the Chi-square test. There were 2, 4, and 4 TB-HIV cases and 2, 6, and 9 TB-T2DM cases during 2019, 2020, and 2021, respectively, whereas there were 2 and 1 DRTB-HIV and DRTB-T2DM cases, respectively. The results indicated that the WHO guidelines for DR-TB were not properly applied to this high-risk population. Hence, the appropriate application of guidelines for TB and DR-TB detection in these patients needs to be immediately implemented by the State health system.

The clinical profile and outcomes of drug resistant tuberculosis in Central Province of Zambia

BackgroundThe emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia.MethodsThis was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital’s Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed.ResultsThe study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36–45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70–0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107–0.638] p = 0.003).ConclusionThe research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.

How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?

A steady increase in the prevalence of drug-resistant tuberculosis (DR-TB) has already been reported in Pakistan. In addition, DR-TB is gradually changing from one-drug resistance to multi-drug resistance, which is a serious challenge for tuberculosis treatment. This review provides an overview of the anti-tuberculosis drugs and focuses on the molecular mechanisms of drug resistance in Mycobacterium tuberculosis, with the hope that it will contribute to the study of drug resistance in response to the emergence of multidrug-resistant tuberculosis.

Genetic diversity of Mycobacterium tuberculosis strains isolated from spiritual holy water site attendees in Northwest Ethiopia. A cross-sectional study

BackgroundThe genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. MethodsA cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Löwenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first-and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. ResultsOf 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%.Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. ConclusionsDiverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.

Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis.

Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs). A facility-based cross-sectional study was conducted in 2020-2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares. Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance. The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.

Prevention of Drug-resistant Tuberculosis

Drug-resistant tuberculosis (TB) poses a significant global health challenge, affecting millions worldwide. Annually, around half a million individuals develop drug-resistant TB, underscoring the urgency of addressing this issue. Treating drug-resistant TB is complex and lengthy, lasting up to two years for a cure. Thus, prevention is the most effective approach to reducing its incidence and prevalence. This paper explores various aspects of drug-resistant TB, providing a holistic understanding of the current knowledge. Firstly, it examines the historical context of drug resistance in TB, tracing its origins and evolution, yielding insights into present challenges. Additionally, the paper elucidates current treatment options, emphasizing the need for a multi-drug approach. The efficacy, limitations, and side effects of these regimens are evaluated, offering a comprehensive overview. Prevention is paramount, and the paper emphasizes its critical importance. Preventive measures such as isoniazid therapy and vaccinations are scrutinized, assessing their efficacy in reducing drug-resistant TB's spread. Global efforts to combat drug-resistant TB, notably the "End TB" strategy by WHO, are highlighted. This plan aims to eradicate TB in all forms, including drug-resistant strains. Understanding its components and objectives provides insight into collective global efforts. Based on historical analysis, current treatment options, prevention strategies, and global efforts, the paper concludes by presenting recommendations for future research and interventions. Ongoing scientific inquiry and innovation are essential for developing more effective treatments, preventive measures, and diagnostics. Furthermore, comprehensive public health interventions encompassing education, awareness campaigns, and strengthened healthcare systems are vital in preventing the spread of drug-resistant TB.

In vitro modeling of isoniazid resistance mechanisms in Mycobacterium tuberculosis H37Rv.

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, has been a global threat to human beings for several decades. Treating tuberculosis has become more difficult as the prevalence of drug-resistant tuberculosis has increased globally. Evidence suggests that the comprehensive landscape of resistance mechanisms in MTB is ambiguous. More importantly, little is known regarding the series of events connected to resistance mechanisms in MTB before exposure to anti-TB drugs, during exposure to the drugs, and finally, when the MTB becomes resistant after exposure, upon analyses of its genome. We used the wild-type strain of MTB (H37Rv) in an in vitro model for generating induced resistance using a sub-inhibitory concentration of isoniazid, and the generated resistance-associated variants (RAVs) were identified using the whole genome sequencing method. The detection of an inhA promoter mutation (fabG1-15C>T), which results in increased production of InhA protein, was found to be a major mechanism for developing resistance to isoniazid in the first place. We observed adaptation of MTB resistance mechanisms in high isoniazid stress by alteration and abolishment of KatG due to the detection of katG S315N, the common region of mutation that confers isoniazid resistance, along with katG K414N, katG N138S, and katG A162E. Furthermore, we detected the ahpC-72C>T and ahpC 21C>A mutations, but further investigation is needed to determine their role in compensating for the loss of KatG activity. This suggests that increased InhA production is the main mechanism where there are low levels of isoniazid, whereas the alteration of KatG was found to be utilized in mycobacterium with a high concentration of isoniazid. Our work demonstrates that this in vitro approach of generating induced resistance could provide clinically relevant information after the fabG1-15C>T mutation, which is the common mutation found in clinical isolates. Moreover, other mutations detected in this work can also be found in clinical isolates. These findings may shed light on the impact of isoniazid in generating RAV and the resistance mechanism scenario that mycobacterium used under various isoniazid-pressuring conditions. More research is needed to understand better the role of RAV and mechanical resistance events within the mycobacterium genome in promoting a promising drug prediction platform that could lead to the right treatment for patients with MDR-TB and XDR-TB.

Epidemic Patterns and Effectiveness of Treatment of Tuberculosis Patients with Different Drug Resistance Profiles in the Republic of Tajikistan

The objective: study of the burden and effectiveness of treatment of multiple drug resistant pulmonary tuberculosis (MDR TB) with different chemotherapy regimens in the Republic of Tajikistan.Subjects and Methods. To achieve this objective, the prevalence of drug resistant tuberculosis in 2009–2020 was studied by analyzing statistical documents on drug resistant tuberculosis, official reporting data from the Center for Medical Statistics and Republican TB Control Center by the Ministry of Health and Population Social Welfare of the Republic of Tajikistan.Results. The analysis of official statistics indicates a stable trend towards a decrease in tuberculosis incidence from 2014 to 2019, annually on average up to 1% – from 60,8 to 56,5 per 100,000 population. During the pandemic in 2019–2020, this trend increased, according to statistics the incidence made 39.7 per 100,000 population. From 2014 to 2019, tuberculosis mortality also declined steadily from 3,9 to 2,2 per 100,000 population. During the pandemic in 2019–2020, a rapid decline was noted – from 2,2 to 1,4, while in 2020–2022, it decreased from 1,4 to 1,0 per 100,000 population. From 2013 to 2020 treatment success reached 90%. The detection of drug resistant tuberculosis is close to 900 cases per year, and more than 90% of them were covered with treatment. In 2018–2020, successful treatment of drug resistant tuberculosis increased from 72,5% to 80,6% due to the introduction of new and repurposed anti-tuberculosis drugs.

Patterns and trends of primary drug-resistant tuberculosis in Chongqing, China, from 2012 to 2020.

Primary drug-resistant tuberculosis (DR-TB) contributes significantly to the global TB epidemic, particularly in countries with high TB burdens. This study aimed to investigate the characteristics of primary DR-TB prevalence in Chongqing, China, from 2012 to 2020. A total of 4546 newly diagnosed and 2769 relapse TB patients admitted to the hospital from 2012 to 2020 were included. Categorical variables were compared using Pearson chi-square test or Fisher exact test, as appropriate. Logistic regression analysis was performed to determine factors associated with primary DR-TB. The rate of primary DR-TB was 24.5%, whereas that of acquired DR-TB was 67.8%. Among newly diagnosed TB cases, the percentage of DR-TB (from 48.9 to 44.2%), mono-resistant TB (from 11.8 to 9.7%), multidrug-resistant TB (MDR-TB; from 25.3 to 6.9%), and pre-extensive drug-resistant TB (from 13.7 to 5.8%) showed a decreasing trend from 2012 to 2020. Age from 15 to 64 years was a risk factor for the development of primary DR-TB (15-44 years: adjusted odds ratio = 2.227, 95% confidence interval: 1.053-4.710; 45-64 years: adjusted odds ratio = 2.223, 95% confidence interval: 1.048-4.717). The rates of primary DR-TB (P = .041) and MDR-TB (P = .007) were significantly higher in the age group of 15 to 64 years than in the age groups of ≤14 years and ≥65 years. Noticeably, rising trends of primary DR-TB (from 0 to 27.3%) and MDR-TB (from 0 to 9.1%) in the population of ≤14 years were observed from 2012 to 2020. Although the rate of primary DR-TB showed a downward trend, a rising drug-resistance rate among some particular subgroups was still observed. Further control of primary DR-TB should focus more on TB patients aged 15 to 64 years.

Identification of seven types of pili in Mycobacterium tuberculosis: Using atomic force microscopy.

Pili are polymeric, hydrophobic, proteinaceous structures generally composed of a major repeating subunit called pilin and, in some cases, a minor tip-associated adhesin subunit. Pili are involved in many virulence-associated functions, such as biofilm formation, adherence, and colonization of mucosal surfaces. Mycobacterium tuberculosis (MTB) strains were isolated from clinically and laboratory-confirmed cases of tuberculosis (TB). The TB isolates were subjected to the Xpert MTB/rifampicin test and then, further susceptibility testing was performed on them against first- and second-line drugs using proportional methods. Thereafter, the selected isolates were subculture in Dubos Tween-albumin liquid culture medium, and at their exponential growth phase (OD600 = 0.05 (5 × 106 colony-forming unit/mL), cells were observed under atomic force microscopy (AFM). For each isolate, 15-20 steel sample packs were prepared and observed under AFM. Here, the data presented are the result of average observation. Under AFM, seven different types of pili were detected, out of which four types, i.e., Type III, Type IV secretion pili, and Type IV-like pili, curli-like pili (MTP) were similar to reported pili in Gram-negative and Gram-positive bacteria. Whereas the other three forms, i.e., Type V (relief funnel pili), Type VI (adhesion tapering), and Type VII (adhesion flap pili), were newly identified and named according to their appearance. Both Types of IV pili were detected in all clinical isolates irrespective of their susceptibility patterns, although significant differences were observed from the side of their protruding. Type Curli pili is similar in appearance in all clinical isolates. Types VI and VII were detected only in extensively drug-resistant and totally drug-resistant-TB isolates (100%). The Type III pili (secretion needle pili) was present in both susceptible- and drug-resistant bacilli, although in drug-resistant strains, we found a considerable difference in their length (50 μ ±10 nm in length) and sometimes, they also had tapering at end. The Type V pili was seen in susceptible isolates but it was at the resting stage (100%; lying aside of cell wall) whereas in drug-resistant isolates, they were getting apart from the cell wall of bacilli with a clear tapering or funnel shape structure. The results of this study highlight the importance of new types of pili expressions in respect of susceptibility patterns in TB. The identified new types of pili would be promising approaches for the treatment and prevention of drug-resistant TB, which needs further investigation.

Expression analysis of efflux gene Rv1634 in drug resistance Mycobacterium tuberculosis isolates

Drug resistant tuberculosis (DR-TB) is a serious health issue worldwide and a number of mechanisms have been suggested which are involved in developing resistance in Mycobacterium tuberculosis to anti-tuberculosis drugs. In the Indian perspective, the pattern and prevalence of drug-resistant tuberculosis (DR-TB) are heterogeneous across regions and settings. Notably, isoniazid (INH), rifampicin (RIF) and ethambutol (EMB) are the most effective drugs in tuberculosis therapy. Understanding the pattern of resistance to these drugs in the Indian population is essential in quick diagnosis of multidrug-resistant (MDR) tuberculosis and extensive DR-TB (XDR-TB). A total of 36 Mycobacterium isolates from the North Indian population were exposed and tested for drug susceptibility with INH, RIF and EMB in vitro and results showed that 25, 24 and 24 isolates were resistant to INH, RIF and EMB respectively. Gene expression analysis revealed that approximately 50% of isolates under the stress of these three anti-tuberculosis drugs showed overexpression of efflux gene Rv1634. Moreover, overexpression of gene Rv1634 contributes to the emergence of drug resistance in M. tuberculosis and inhibition of Rv1634 along with other efflux pump genes and may provide a promising strategy for improving tuberculosis treatment outcomes in North India.

Mycobacterium tuberculosis Drug Resistance in Ethiopia: An Updated Systematic Review and Meta-Analysis.

Background: Tuberculosis (TB) remains a significant global public health issue, despite advances in diagnostic technologies, substantial global efforts, and the availability of effective chemotherapies. Mycobacterium tuberculosis, a species of pathogenic bacteria resistant to currently available anti-TB drugs, is on the rise, threatening national and international TB-control efforts. This systematic review and meta-analysis aims to estimate the pooled prevalence of drug-resistant TB (DR-TB) in Ethiopia. Materials and Methods: A systematic literature search was undertaken using PubMed/MEDLINE, HINARI, the Web of Science, ScienceDirect electronic databases, and Google Scholar (1 January 2011 to 30 November 2020). After cleaning and sorting the records, the data were analyzed using STATA 11. The study outcomes revealed the weighted pooled prevalence of any anti-tuberculosis drug resistance, any isoniazid (INH) and rifampicin (RIF) resistance, monoresistance to INH and RIF, and multidrug-resistant TB (MDR-TB) in newly diagnosed and previously treated patients with TB. Results: A total of 24 studies with 18,908 patients with TB were included in the final analysis. The weighted pooled prevalence of any anti-TB drug resistance was 14.25% (95% confidence interval (CI): 7.05–21.44%)), whereas the pooled prevalence of any INH and RIF resistance was found in 15.62% (95%CI: 6.77–24.47%) and 9.75% (95%CI: 4.69–14.82%) of patients with TB, respectively. The pooled prevalence for INH and RIF-monoresistance was 6.23% (95%CI: 4.44–8.02%) and 2.33% (95%CI: 1.00–3.66%), respectively. MDR-TB was detected in 2.64% (95%CI: 1.46–3.82%) of newly diagnosed cases and 11.54% (95%CI: 2.12–20.96%) of retreated patients with TB, while the overall pooled prevalence of MDR-TB was 10.78% (95%CI: 4.74–16.83%). Conclusions: In Ethiopia, anti-tuberculosis drug resistance is widespread. The estimated pooled prevalence of INH and RIF-monoresistance rates were significantly higher in this review than in previous reports. Moreover, MDR-TB in newly diagnosed cases remained strong. Thus, early detection of TB cases, drug-resistance testing, proper and timely treatment, and diligent follow-up of TB patients all contribute to the improvement of DR-TB management and prevention. Besides this, we urge that a robust, routine laboratory-based drug-resistance surveillance system be implemented in the country.

Temporal trend of drug-resistant tuberculosis among Thai children during 2006–2021

BackgroundThe prevalence of drug-resistant tuberculosis (DR-TB) in adults has stabilized in the past decade. Our study aimed to describe the prevalence of DR-TB in Thai children between 2006 and 2021. Materials and methodsChildren younger than 15 years old who had culture-confirmed Mycobacterium tuberculosis complex (MTB), positive PCR-MTB, or positive Xpert MTB/RIF were included in this cohort. Drug susceptibility testing (DST) was performed using phenotypic and/or genotypic methods. The prevalence of DR-TB was compared using the chi-square test. ResultsAmong 163 confirmed TB cases (44% as pulmonary TB, 27% as extrapulmonary TB, and 29% with both), the median age (IQR) was 12.2 (7.3–14.2) years. DST was performed in 139 cases (85%), revealing prevalences of all DR-TB, isoniazid-resistant TB (Hr-TB), and rifampicin monoresistant/multidrug-resistant TB (Rr/MDR-TB) of 21.6% (95% CI 14.7–28.4), 10.8% (95% CI 5.6–16.0%), and 2.9% (95% CI 0.1–5.7%), respectively. The DR-TB rates did not differ significantly between 2006–2013, 2014–2018, and 2019–2021 (p > 0.05). Two pre-extensively DR-TB (pre-XDR) cases with fluoroquinolone resistance were detected after 2014. ConclusionThe prevalence of DR-TB in Thai children was stable. However, one-tenth of DR-TB cases confirmed with DST were Hr-TB, which required adjustment of the treatment regimen. The pre-XDR cases should be closely monitored.

Patterns of Presentation of Drug-Resistant Tuberculosis in Nigeria: A Retrospective File Review

Background: An understanding of the patterns of drug-resistant tuberculosis (DR-TB) is needed to develop the best diagnostic tools and decide on optimal treatment combination therapies for the management of DR-TB in Nigeria. Objective: We aimed to investigate patterns of DR-TB for the five first-line anti-TB drugs over a period of seven years (2010–2016) and the associated clinical and socio-demographic factors. Methods: A retrospective study recruited 2555 DR-TB patients between 2010 and 2016 across the six geopolitical treatment zones in Nigeria. We determined DR-TB patterns based on standard case definition and their association with demographic and clinical information. Data were analyzed using Statistical Package for Social Sciences (SPSS) software. Independent predictors of DR-TB patterns/types were determined using bivariate and multivariate analyses with a statistical significance of p < 0.05 and a 95% confidence interval. Results: The majority of the participants were males, 66.93% (1710), 31–40 years old, 35.19% (899), previously treated, 77.10% (1909), had received at least two treatments, 411 (49.94%) and were multi-drug resistant, 61.41% (1165). The Southwest zone had the highest number of DR-TB cases, 36.92%. We found an upward trend in the prevalence of DR-TB from 2010 to 2016. Participants who had received one previous treatment showed statistically significant higher rifampicin resistance (59.68%), those with two previous treatments reported a statistically significant higher polydrug resistance (78.57%), and those with three or more previous treatments had a statistically significant higher multidrug resistance (19.83%) (χ2 = 36.39; p = 0.001). Mono-drug resistance and rifampicin resistance were statistically significantly higher in the southwest zone (29.48% and 34.12% respectively), polydrug resistance in the northcentral (20.69%) and south-south zones (20.69%), and multidrug resistance in the southwest (30.03%) and northcentral zones (19.18%) (χ2 = 98.26; p = 0.001). Conclusions: We present patterns of DR-TB across the six geopolitical zones in Nigeria. Clinicians should weigh in on these patterns while deciding on the best first-line drug combinations to optimize treatment outcomes for DR-TB patients. A national scale-up plan for DST services should focus on patients with previous multiple exposures to anti-TB treatments and on those in the Northeastern zone of the country.

Drug Resistance Patterns and Trends in Patients with Suspected Drug-Resistant Tuberculosis in Dalian, China: A Retrospective Study.

PurposeThe emergence of drug-resistant tuberculosis (DR-TB) represents a threat to the control of tuberculosis. This study aimed to estimate the patterns and trends of DR-TB in patients with suspected DR-TB. In addition, risk factors for multidrug-resistant tuberculosis (MDR-TB) were identified among suspected DR-TB patients in Dalian, China.Patients and MethodsA total of 5661 patients with suspected DR-TB from Jan 1, 2013 to Dec 31, 2020 were included in the final analysis. The resistance pattern of all resistant strains was determined by drug susceptibility testing (DST) using the conventional Lowenstein-Jensen Proportion Method (LJ). DR-TB trends were estimated from 2013 to 2020. During the research period, the chi-square test was employed to analyze the significance of linear drug-resistance trends across time. Bivariate and multivariate logistic regression were performed to assess factors associated with MDR-TB.ResultsFrom 2013 to 2020, the resistance rates of rifampicin (RFP) and isoniazid (INH) decreased significantly, whereas the resistance rates of ethambutol (EMB) and streptomycin (SM) increased in patients with suspected DR-TB. From 2013 to 2020, the prevalence of DR-TB decreased in all patients from 34.71% to 28.01% with an average annual decrease of 3.02%. Among new cases, from 2013 to 2020, the prevalence of DR-TB (from 26.67% to 24.75%), RFP-resistant TB (RR-TB) (from 15.09% to 3.00%) and MDR-TB (from 6.08% to 2.62%) showed a significant downward trend. Among patients with a previous treatment history, DR-TB (from 54.70% to 37.50%), RR-TB (from 44.16% to 11.49%) and MDR-TB (from 26.90% to 10.34%) showed a significant downward trend from 2013 to 2020. Males (AOR 1.28, 95% CI 1.035–1.585), patients 45 to 64 years of age (AOR 1.75, 95% CI 1.342–2.284), patients 65 years and older (AOR 1.65, 95% CI 1.293–2.104), rural residents (AOR 1.24, 95% CI 1.014–1.519) and a previous treatment history (AOR 3.94, 95% CI 3.275–4.741) were risk factors for MDR-TB.ConclusionThe prevalence of DR-TB, RR-TB and MDR-TB was significantly reduced from 2013 to 2020. Considerable progress has been made in the prevention and treatment of DR-TB during this period. However, the increasing rate of drug resistance in EMB and SM should be taken seriously. Suspected DR-TB patients who are male, older than 45 years of age, live in rural areas, and have a history of TB treatment should be given priority by health care providers.

Pattern of drug resistant Mycobacterium tuberculosis in the west and northwest of Iran: a meta-analysis.

Drug-resistant tuberculosis (Tb) is a major public health issue across the world. Therefore, it is crucial to determine its pattern in different regions of the world. The aim of this study was to review the prevalence of drug resistant TB in the west and northwest of Iran. A systematic literature search was performed to identify studies (2010 to 2021) in Google Scholar, PubMed, Thomson Reuters, Scientific Information Database (SID), Cochrane Library, and Medical Library (MedLib) databases. The patterns of any drug-resistant Mycobacterium tuberculosis (MTB); resistance to isoniazid (INH), rifampicin (RMP), streptomycin (SMP), ethambutol (EMB), and multiple drug resistance (MDR) were reviewed in tuberculosis in the west and northwest of Iran. In this review, 7 studies met the eligibility criteria for a meta-analysis. The pooled proportion of any drug resistant TB was 13% (CI 95%: 9.0, 17.0) (43.0% in re-treatment group). The pooled prevalence of any drug resistant TB was more than 1.5 times higher in men compared to women (15% vs. 9.0%). The pooled prevalence (%) of resistance to INH, RMP, SMP, EMB and MDR-TB was 11.0%, 12.0%, 13.0%, 6.0%, and 6.0%, respectively. Kermanshah Province (a province in the west of Iran) showed a high prevalence of any type of drug resistance and MDR-TB (15.9% and 20.0%, respectively). It seems that the western provinces of Iran have a different pattern of drug resistance compared to the northwestern provinces. Considering the extent of Iran and the neighboring countries, it is recommended that the pattern of tuberculosis drug resistance be reviewed separately in different provinces or regions of Iran. Drug resistance in the re-treatment group was more than three times that of all patients with TB drug resistance. The burden of drug resistance reduces significantly with better control and management of TB drug treatment and preventing re-infection.

Characteristics and Trend of Drug-Resistant Tuberculosis at a Major Specialized Hospital in Chongqing, China: 2016 Versus 2019.

The epidemic of drug-resistant tuberculosis (DR-TB) has become a major concern in global TB control. This study aimed to investigate the patterns and trend of DR-TB epidemic between different time periods in Chongqing. A total of 985 and 835 culture positive TB patients with drug susceptibility testing (DST) results admitted to the hospital in 2016 and 2019, respectively, were included. Chi-square testing was used to compare the prevalence and trends of DR-TB in 2016 and 2019. The proportion of previously treated TB cases with culture positivity was 45.7% in 2019, significantly higher than that in 2016 (39.1%, P = 0.004). The overall rate of drug resistance in 2019 was 43.1%, higher than that in 2016 (40.2%). The rates of multi-drug resistant TB (MDR-TB) and pre-extensively drug resistant TB (pre-XDR-TB) increased significantly from 2016 to 2019 among all TB cases (MDR: 25% vs 33.4%, P < 0.001 and pre-XDR: 7.1% vs 12.8%, P < 0.001, respectively) and previously treated TB cases (MDR: 46.5% vs 56%, P = 0.008 and pre-XDR: 13.2% vs 21.5%, P = 0.003, respectively). Our findings indicated that the prevalence of DR-TB remains high in Chongqing. The trend of resistance to anti-TB drugs beccame worse between 2016 and 2019. Moreover, acquired MDR may play a major role in MDR-TB epidemic in Chongqing. Therefore, rapid diagnosis and effective treatment of TB patients will be important to reduce the burden of DR-TB in Chongqing.

Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea.

BackgroundMolecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG.MethodsWe performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015).ResultsSampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier.ConclusionsThe acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-022-07414-2.

Isoniazid and Rifampicin Tuberculosis Drug Resistance in HIV Endemic Region of Western Kenya

Background: Tuberculosis drug resistance is often associated with inadequate anti-tuberculosis treatment regimen resulting to mutations that confers resistance to anti-tuberculosis agents. This is aggravated by synergetic relationship between Tuberculosis and HIV (Human Immunodeficiency Virus). Over 25% of Global Tuberculosis deaths occur in Africa and Kenya is one of the 30 high burden countries that together account for more than 80% of the world’s TB cases. According to World Health Organization, in 2018, Multi drug resistant Tuberculosis prevalence in Kenya was 1.3% in new cases and 4.4% in retreatment cases. Kisumu County recorded the second highest HIV prevalence at 18.6% against the national prevalence of 4.5% in 2020. The extent of regional burden of DR-TB and HIV co-infection has not been exactly well-defined in Western Kenya. Methods: This was a prospective cross sectional study that aimed to explore the association between Tuberculosis drug resistance and HIV status among new and previously treated pulmonary tuberculosis cases in Kisumu County, Kenya. Tuberculosis clinical suspects were recruited into the study and classified as HIV positive or negative based on their clinical data. Sputum samples from tuberculosis clinical suspects were subjected to fluorescent microscopy, phenotypic culture and line probe assay. Results: Out of a sample of 256, response rate was 216 of which HIV positive cases were 119(55.1%) and negative were 97 (44.9%). The study found that out of 11 that were phenotypic Isoniazid resistance 8(6.7%) were from HIV positive cases while 3 (3.2%) were from HIV negative cases. Phenotypic rifampicin resistance among the HIV positive were 8 (6.7%) while HIV negative were 2 (2.1%). All the 2(1.7%) MDR cases were from HIV positive participants. The study found out that HIV status and Tuberculosis cases were significantly associated at p&lt;.05. HIV positive cases were more likely associated with retreatment cases (OR=1.4,95CI:1.00-1.90) compared to new cases. The study found out that the common mutant probe among the HIV positive was katG MUT1 4(2.6%), while mutant probes among the HIV negative were in hA MUT1 1(0.7%), katG MUT1 1(0.7%) and roB MUT2A 1(0.7%). Wild type gene deletion among the HIV positive cases were observed in probes katG WT 3(2.1%), roB WT7, katG WT 1(0.7%) while wild type gene deletion among the HIV negative cases were inhA WT1 1(0.7%), in hA WT1/inhAWT2 1(0.7%), katG WT 1(0.7%). Conclusion: Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis drug resistance transmission. Development and improvement of the efficacy of interventions will require a greater understanding of the transmission of multidrug-resistant tuberculosis in HIV-endemic settings like Kisumu County, Western Kenya.

Mathematical analysis of a two-strain tuberculosis model in Bangladesh

Tuberculosis (TB) is an airborne infectious disease that causes millions of deaths worldwide each year (1.2 million people died in 2019). Alarmingly, several strains of the causative agent, Mycobacterium tuberculosis (MTB)—including drug-susceptible (DS) and drug-resistant (DR) variants—already circulate throughout most developing and developed countries, particularly in Bangladesh, with totally drug-resistant strains starting to emerge. In this study we develop a two-strain DS and DR TB transmission model and perform an analysis of the system properties and solutions. Both analytical and numerical results show that the prevalence of drug-resistant infection increases with an increasing drug use through amplification. Both analytic results and numerical simulations suggest that if the basic reproduction numbers of both DS ({text{R}}_{{0{text{s}}}}) and DR ({text{R}}_{{0{text{r}}}}) TB are less than one, i.e. max left[ {{text{R}}_{{0{text{s}}}} ,{text{ R}}_{{0{text{r}}}} } right] < 1, the disease-free equilibrium is asymptotically stable, meaning that the disease naturally dies out. Furthermore, if {text{R}}_{{0{text{r}}}} > {text{max}}left[ {{text{R}}_{{0{text{s}}}} ,1} right], then DS TB dies out but DR TB persists in the population, and if {text{R}}_{{0{text{s}}}} > {text{max}}left[ {{text{R}}_{{0{text{r}}}} ,1} right] both DS TB and DR TB persist in the population. Further, sensitivity analysis of the model parameters found that the transmission rate of both strains had the greatest influence on DS and DR TB prevalence. We also investigated the effect of treatment rates and amplification on both DS and DR TB prevalence; results indicate that inadequate or inappropriate treatment makes co-existence more likely and increases the relative abundance of DR TB infections.