Anti-tuberculosis Drug Resistance Research Articles

Diagnostic accuracy of the Xpert® MTB/XDR assay for detection of Isoniazid and second-line antituberculosis drugs resistance at central TB reference laboratory in Tanzania

IntroductionEarly diagnosis of tuberculosis (TB) and universal access to drug-susceptibility testing (DST) are critical elements of the WHO End TB Strategy. Current rapid tests (e.g., Xpert® MTB/RIF and Ultra-assays) can detect rifampicin resistance-conferring mutations, but cannot detect resistance to Isoniazid and second-line anti-TB agents. Although Line Probe Assay is capable of detecting resistance to second-line anti-TB agents, it requires sophisticated laboratory infrastructure and advanced skills which are often not readily available in settings replete with TB. A rapid test capable of detecting Isoniazid and second-line anti-TB drug resistance is highly needed.MethodsWe conducted a diagnostic accuracy study to evaluate a new automated Xpert MTB/XDR 10-colour assay for rapid detection of Isoniazid and second-line drugs, including ethionamide, fluoroquinolones, and injectable drugs (Amikacin, Kanamycin, and Capreomycin). Positive Xpert MTB/RIF respiratory specimens were prospectively collected through routine diagnosis and surveillance of drug resistance at the Central TB Reference Laboratory in Tanzania. Specimens were tested by both Xpert XDR assay and LPA against culture-based phenotypic DST as the reference standard.FindingsWe analysed specimens from 151 TB patients with a mean age (SD) of 36.2 (12.7) years. The majority (n = 109, 72.2%) were males. The sensitivity for Xpert MTB/XDR was 93.5% (95% CI, 87.4–96.7); for Isoniazid, 96.6 (95% CI, 92.1–98.6); for Fluoroquinolone, 98.7% (95% Cl 94.8–99.7); for Amikacin, 96.6%; and (95% CI 92.1–98.6) for Ethionamide. Ethionamide had the lowest specificity of 50% and the highest was 100% for Fluoroquinolone. The diagnostic performance was generally comparable to that of LPA with slight variations between the two assays. The non-determinate rate (i.e., invalid M. tuberculosis complex detection) of Xpert MTB/XDR was 2·96%.ConclusionThe Xpert MTB/XDR demonstrated high sensitivity and specificity for detecting resistance to Isoniazid, Fluoroquinolones, and injectable agents. This assay can be used in clinical settings to facilitate rapid diagnosis of mono-isoniazid and extensively drug-resistant TB.

Epidemiology of first-and second-line anti-tuberculosis drug resistance profile in new pulmonary tuberculosis cases in addis ababa metropolitan area, ethiopia

Epidemiology of first-and second-line anti-tuberculosis drug resistance profile in new pulmonary tuberculosis cases in addis ababa metropolitan area, ethiopia

Diagnostic efficacy of an optimized nucleotide MALDI-TOF-MS assay for anti-tuberculosis drug resistance detection.

We aimed at evaluating the diagnostic efficacy of a nucleotide matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) assay to detect drug resistance of Mycobacterium tuberculosis. Overall, 263M. tuberculosis clinical isolates were selected to evaluate the performance of nucleic MALDI-TOF-MS for rifampin (RIF), isoniazid (INH), ethambutol (EMB), moxifloxacin (MXF), streptomycin (SM), and pyrazinamide (PZA) resistance detection. The results for RIF, INH, EMB, and MXF were compared with phenotypic microbroth dilution drug susceptibility testing (DST) and whole-genome sequencing (WGS), and the results for SM and PZA were compared with those obtained by WGS. Using DST as the gold standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 98.2%, 98.7%, and 0.97 for RIF; 92.8%, 99%, and 0.90 for INH; 82.4%, 98.0%, and 0.82 for EMB; and 92.6%, 99.5%, and 0.94 for MXF, respectively. Compared with WGS as the reference standard, the sensitivity, specificity, and kappa values of the MALDI-TOF-MS assay for the detection of resistance were 97.4%, 100.0%, and 0.98 for RIF; 98.7%, 92.9%, and 0.92 for INH; 96.3%, 100.0%, and 0.98 for EMB; 98.1%, 100.0%, and 0.99 for MXF; 98.0%, 100.0%, and 0.98 for SM; and 50.0%, 100.0%, and 0.65 for PZA. The nucleotide MALDI-TOF-MS assay yielded highly consistent results compared to DST and WGS, suggesting that it is a promising tool for the rapid detection of sensitivity to RIF, INH, EMB, and MXF.

Molecular Analysis of Anti-Tuberculosis Drug Resistance of Mycobacterium tuberculosis Isolated in the Republic of Korea.

Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB Ser531Leu, katG Ser315Thr, and gyrA Asp94Gly; however, the minimum inhibitory concentrations varied, which can be attributed to other resistance mechanisms. Examination of genetic relatedness among drug-resistant isolates revealed that the cluster size of resistant bacteria was less than six strains, suggesting no evidence of a large-scale epidemic caused by a specific strain. However, rpoC mutants of the rifampicin-resistant isolates were composed of five types of clusters, suggesting that these compensatory mutations advance propagation. In the present study, more than 90% of the resistance mechanisms to major anti-TB drugs were identified, and the effect of each mutation on drug resistance was estimated. With the clinical application of recent next-generation sequencing-based susceptibility testing, the present study is expected to improve the clinical utilization of genotype-based drug susceptibility testing for the diagnosis and treatment of patients with drug-resistant TB.

Mycobacterium tuberculosis Gene Expression Associated With Fluoroquinolone Resistance and Efflux Pump Inhibition.

We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene expression and expression quantitative trait loci (eQTL). We determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant and -susceptible Mtb isolates without and with the efflux pump inhibitor verapamil. We performed RNA sequencing (RNA-seq), whole genome sequencing (WGS), and eQTL analysis, focusing on efflux pump, transport, and secretion-associated genes. Of 42 ofloxacin-resistant Mtb isolates, 27 had adequate WGS coverage and acceptable RNA-seq quality. Of these 27, 7 had >2-fold reduction in ofloxacin MIC with verapamil; 6 had 2-fold reduction, and 14 had <2-fold reduction. Five genes (including Rv0191) had significantly increased expression in the MIC fold change >2 compared to <2 groups. Among regulated genes, 31 eQTLs (without ofloxacin) and 35 eQTLs (with ofloxacin) had significant allele frequency differences between MIC fold change >2 and <2 groups. Of these, Rv1410c, Rv2459, and Rv3756c (without ofloxacin) and Rv0191 and Rv3756c (with ofloxacin) have previously been associated with antituberculosis drug resistance. In this first reported eQTL analysis in Mtb, Rv0191 had increased gene expression and significance in eQTL analysis, making it a candidate for functional evaluation of efflux-mediated fluoroquinolone resistance in Mtb.

Clinical Evaluation of the XDR-LFC Assay for the Molecular Detection of Isoniazid, Rifampin, Fluoroquinolone, Kanamycin, Capreomycin, and Amikacin Drug Resistance in a Prospective Cohort.

While the goal of universal drug susceptibility testing has been a key component of the WHO End TB Strategy, in practice, this remains inaccessible to many. Rapid molecular tests for tuberculosis (TB) and antituberculosis drug resistance could significantly improve access to testing. In this study, we evaluated the accuracy of the Akonni Biosystems XDR-TB (extensively drug-resistant TB) TruArray and lateral-flow-cell (XDR-LFC) assay (Akonni Biosystems, Inc., Frederick, MD, USA), a novel assay that detects mutations in seven genes associated with resistance to antituberculosis drugs: katG, the inhA promoter, and the ahpC promoter for isoniazid; rpoB for rifampin; gyrA for fluoroquinolones; rrs and the eis promoter for kanamycin; and rrs for capreomycin and amikacin. We evaluated assay performance using direct sputum samples from 566 participants recruited in a prospective cohort in Moldova over 2 years. The sensitivity and specificity against the phenotypic reference were both 100% for isoniazid, 99.2% and 97.9% for rifampin, 84.8% and 99.1% for fluoroquinolones, 87.0% and 84.1% for kanamycin, 54.3% and 100% for capreomycin, and 79.2% and 100% for amikacin, respectively. Whole-genome sequencing data for a subsample of 272 isolates showed 95 to 99% concordance with the XDR-LFC-reported suspected mutations. The XDR-LFC assay demonstrated a high level of accuracy for multiple drugs and met the WHO's minimum target product profile criteria for isoniazid and rifampin, while the sensitivity for fluoroquinolones and amikacin fell below target thresholds, likely due to the absence of a gyrB target in the assay. With optimization, the XDR-LFC shows promise as a novel near-patient technology to rapidly diagnose drug-resistant tuberculosis.

First and Second-Line Anti-Tuberculosis Drug-Resistance Patterns in Pulmonary Tuberculosis Patients in Zambia.

Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study. A total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants' social-demographic characteristics were obtained using a pre-test checklist. Overall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5-31.6%). A total of 9.8% (13/132, 95% CI: 5.3-16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3-16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1-146.5%) to have drug-resistant TB than those who had no history of being treated for TB. This study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring.

Evaluation Study of xMAP TIER Assay on a Microsphere-Based Platform for Detecting First-Line Anti-Tuberculosis Drug Resistance

Early diagnosis of drug susceptibility for tuberculosis (TB) patients could guide the timely initiation of effective treatment. We evaluated a novel multiplex xMAP TIER (Tuberculosis-Isoniazid-Ethambutol-Rifampicin) assay based on the Luminex xMAP system to detect first-line anti-tuberculous drug resistance. Deoxyribonucleic acid samples from 353 Mycobacterium tuberculosis clinical isolates were amplified by multiplex polymerase chain reaction, followed by hybridization and analysis through the xMAP system. Compared with the broth microdilution method, the sensitivity and specificity of the xMAP TIER assay for detecting resistance was 94.9% (95%CI, 90.0-99.8%) and 98.9% (95%CI, 97.7-100.0%) for rifampicin; 89.1% (95%CI, 83.9-94.3%) and 100.0% (95%CI, 100.0-100.0%) for isoniazid; 82.1% (95% CI, 68.0-96.3%) and 99.7% (95% CI, 99.0-100.0%) for ethambutol. With DNA sequencing as the reference standard, the sensitivity and specificity of xMAP TIER for detecting resistance were 95.0% (95% CI, 90.2-99.8%) and 99.6% (95% CI, 98.9-100.0%) for rifampicin; 96.9% (95% CI, 93.8-99.9%) and 100.0% (95% CI, 100.0-100.0%) for isoniazid; 86.1% (95% CI, 74.8-97.4%) and 100.0% (95% CI, 100.0-100.0%) for ethambutol. The results achieved showed that the xMAP TIER assay had good performance for detecting first-line anti-tuberculosis drug resistance, and it has the potential to diagnose drug-resistant tuberculosis more accurately due to the addition of more optimal design primers and probes on open architecture xMAP system.

An overview of the pattern of first- and second-line anti-tuberculosis drug resistance gene mutations

Tuberculosis is still the most prevalent infectious cause of mortality, and it has a significant medical, societal, and economic impact MDR-TB is a type of tuberculosis (TB) infection produced by bacteria resistant to at least two of the most important first-line anti-TB treatments, isoniazid, and rifampin. Extensively drug-resistant tuberculosis (XDR-TB) is a type of tuberculosis that is resistant to second-line treatments. MDR-TB is a type of tuberculosis (TB) infection produced by bacteria resistant to at least two of the most important first-line anti-TB treatments, isoniazid, and rifampin. Extensively drug-resistant tuberculosis (XDR-TB) is a type of tuberculosis that is resistant to second-line treatments. Because resistant cases have significant morbidity and mortality, multidrug-resistant tuberculosis poses a significant threat to treatment. The most effective anti-tuberculosis drugs are first-line essential anti-tuberculosis drugs, which must be included in any short-term treatment plan. Rifampicin, ethambutol, Isoniazid, streptomycin, and pyrazinamide are among the medications in this group. Ethionamide, amikacin, capreomycin, and para-aminosalicylic acid are Second-line anti-tuberculosis that are clinically ineffective and cause severe responses far more commonly than first-line drugs. Resistance to first-line drugs was connected to mutations in the pncA, emb­­­­, rpsL, and rrs genes, while rrs, gyrA, eis, tlyA and gryB are associated with second-line drugs.

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.

The Emergence of Novel Spoligotypes of Highly Drug-Resistant Mycobacterium tuberculosis Isolates in Fujian, China.

BackgroundHere, we aimed to determine the population structure of Mycobacterium tuberculosis (MTB) genotypes in Fujian and explore risk factors associated with infection with the Beijing genotype. We also explored the association between Beijing genotype and drug resistance.MethodsRepresentative MTB isolates obtained during provincial-level routine anti-tuberculosis drug resistance surveillance conducted since 2013 in 11 Fujian counties were analyzed using McSpoligotyping. In vitro drug susceptibilities to anti-tuberculosis drugs were determined using the standard Löwenstein–Jensen proportion method.ResultsOverall, 477 MTB isolates were included in the study, of which 245 isolates belonged to the Beijing genotype family and 232 possessed non-Beijing genotypes. Ultimately, a total of 204 spoligotypes were identified that included 58 spoligotype international types (SITs) from the SITVITWEB database and 146 novel spoligotypes. As compared to patients <25 years of age (control group), elderly patients (≥65 years of age) were more likely to be infected with non-Beijing genotypes [aOR 18.69, 95% CI (5.80–60.26)], with risk of infection with non-Beijing genotypes increasing with age [aOR 3.73, 95% CI (1.67–8.30) for patients 45–64 years of age]. Additionally, as compared to isolates with Beijing and other non-Beijing genotypes, significantly greater proportions of isolates with novel spoligotypes exhibited PTO- and PAS-resistance. Moreover, a markedly higher proportion of isolates with novel spoligotypes exhibited OFX-resistance as compared to isolates with other non-Beijing genotypes.ConclusionOur data demonstrated that the Beijing genotype is the predominant MTB sublineage in Fujian and that the prevalence rate of infection with this MTB genotype decreases with advancing patient age. Notably, the prevalence rate of this genotype in Fujian TB patients is relatively lower than in other regions of China. In addition, the emergence of novel spoligotypes of highly drug-resistant MTB isolates highlights the urgent need for ongoing molecular genotyping surveillance in Fujian.

Multidrug Resistant Tuberculosis: Trends and Control

Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to the control of tuberculosis (TB). The exact magnitude of problem of resistance to anti-tuberculosis drugs worldwide was not known till the 1994-97 global project on anti-tuberculosis drug resistance surveillance initiated by the World Health Organization (WHO) and International Union Against Tuberculosis and Lung Diseases (IUATLD). The Global Tuberculosis Report 2014 estimated that an 3.5% of newly diagnosed and 20.5% of previously treated.TB cases had MDR-TB. It has been estimated that 480,000 cases emerged and 210,000 deaths occurred due to MDR-TB globally in 2013. In India, estimates showed that the prevalence of MDR-TB among new and previously treated patients was 2.2% and 15%, respectively. It is estimated that 99,000 cases of MDR-TB emerge every year of which 62,000 were among notified cases of TB in 2013. The MDR-TB is a human-made problem and results largely from poorly managed cases of TB. Adequate, timely diagnosis and optimal treatment of MDR-TB will help curb the epidemic. Efforts must be focused on the effective use of anti-tuberculosis drugs in every new patient, so as to prevent the emergence of MDR-TB.

Spoligotype-based population structure and isoniazid-resistance gene mutation of Mycobacterium tuberculosis isolates from Thailand

The present study aims to investigate the population structure of Thai Mycobacterium tuberculosis (MTB) isolates and anti-tuberculosis (TB) drug resistance and to determine the most frequent genetic mutations conferring isoniazid (INH) resistance. Genomic DNA from 287 MTB clinical isolates were extracted and used for spoligotyping, amplification and sequencing analysis of the region of different (RD) 105, and of the INH resistance (IR) associated genes, inhA, katG and oxyR-ahpC genes. Eighty-one clinical isolates were resistant to at least one first-line drug; 53 of these were resistant to INH. All strains were classified into three lineages based on their spoligotypes: East Asia (EA)/Beijing, Indo-Oceanic (IO), and Euro-American (EuA). EA and IO lineages revealed a strong association with anti-TB drug resistance (P=0.005 and 0.013, respectively). A total of 33 mutations were found among IR isolates, which for 28 (84.8%), 3 (9.1%), and 2 (6.1%) occurred in katG, inhA, and oxyR-ahpC genes, respectively. Moreover, the most common mutations found were 54.7% of IR presented Ser315Thr at katG (54.7%) and C-15T at inhA (15.1%) presented. This result suggests the involvement of other genetic markers or other mechanisms of resistance. This study provides information about strains diversity, drug resistance profiles, and their possible association. EA and IO lineages were predominant in Thailand, and they were highly associated with anti-TB drug resistance. Testing two mutations including katGSer315Thr and inhA-15C→T could detect 68% of the IR strains.

First-Line Anti-Tuberculosis Drug Resistance Pattern

Introduction: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis and usually attacks the lungs. Indonesia is in the third rank of TB cases in the world. An important concern regarding TB currently is the case of anti-TB drug resistance, hence research on resistance patterns and risk factors is essential. This study aimed to identify the pattern of first-line anti-TB drug resistance at Dr. Soetomo General Hospital, Surabaya.Methods: A descriptive retrospective study was conducted at Dr. Soetomo General Hospital, Surabaya for the period of 2017-2019. The samples were obtained through total population sampling of 239 pulmonary TB patients with first-line anti-TB drug resistance which were registered at MDR-TB Polyclinic Dr. Soetomo General Hospital, Surabaya. Only complete medical records were included. The variables were first-line anti-TB drug resistance (isoniazid, rifampicin, ethambutol, streptomycin) and patients’ characteristics (age, gender, treatment history, and comorbidities). The drug resistance test was performed using certified culture methods.Results: Among 239 patients, the incidences of resistance to H, R, E, and S were 79.08%, 94.14%, 25.94%, and 20.08%, respectively. The most common patterns were HR (42.26%), R (18.83%), and HRE (12.55%). The largest age group was 45-54 years old (38%). The dominant gender was male (56.49%). The most treatment history category was relapsed patients (48%) and there were more patients with comorbidity (57%).Conclusion: The highest incidence rate of resistance was rifampicin and the most common resistance pattern was HR. Most of the patients were of working age, male, relapse patients, and had comorbidities. An appropriate TB therapy treatment plays an important role in preventing resistance.

The evaluation of second line drug susceptibilities and molecular epidemiological profiles of multidrug resistance Mycobacterium tuberculosis isolates isoleted from different region of Turkey

Introduction: This study was planned to determine the second line drug resistance and molecular epidemiological profiles of multidrug resistant Mycobacterium tuberculosis isolates isolated from different geographical regions of Turkey.&#x0D; Material and Method: In our study, 63 MDR M. tuberculosis isolates were evaluated for the drug susceptibility sent from different tuberculosis laboratories of Turkey. Secondary antituberculosis drugs resistance was evaluated by indirect proportion method. Epidemiological origins were evaluated by using IS6110-RFLP and spoligotyping methods. &#x0D; Results: Cycloserine, ethionamide, capreomycin, thiacetozone, ofloxacin, kanamsin and paraaminosalicylic acid resistance rates were 15.87%, 19.04%, 7.93%, 6.34%, 11.11%, 12.69% and 6.34.%, respectively. According to spoligotyping results, 11 different patterns were obtained, including 52 isolates consisting of 5 clusters and 11 patterns consisting of a single isolate. When we compared our results with the spoligotype database in the world; 42 of 52 isolates forming 5 clusters were identified as predefined spoligotypes (LAM7-TUR, LAM9, T clade). 10 isolates showed the characteristics of the U spoligotype family. Of the 11 isolates that produced 11 different patterns, 8 were Haarlem and T spoligotypes. It was found that 2 isolates had the characteristics of Orphan and 1 isolate had the characteristics of BOV family. &#x0D; Conclusion: In our study, LAM7-TUR, LAM9, T clade spoligotype families are common in our country and in the world were determined.

Factors Associated with Treatment Failure for Microscopy-positive Pulmonary Tuberculosis at the General Reference Hospital of Beni (DR Congo) between 2010 and 2020: Case-control Study

Introduction: Failure to treat microscopy-positive pulmonary tuberculosis (MPT+) poses a risk to public health through the spread of infection and could be a gateway to anti-tuberculosis drug resistance. The aim of this study was to describe the epidemiological characteristics of PMT+ TB patients with treatment failure, to measure the degree of association between the various factors and TB treatment failure, and to formulate recommendations for improving NTP activities.&#x0D; Methods: This is a retrospective case-control study conducted from 1 January 2010 to 31 December 2020 at the CDTMR of the General Referral Hospital of Beni. The cases are patients treated for PMT+ and who had a therapeutic failure. Three controls for each case were selected among patients with PMT+ who were declared cured. Data analysis was performed using Epi-Info version 3.5.3 for Windows.&#x0D; Results: 128 patients were included in the study. 32 patients were treatment failures. The mean age of cases and controls was 42 years (+/- 14), the M/F sex ratio was 31 and 2.4 in cases and controls respectively, urban residents accounted for 90.3% and 83.2% in cases and controls respectively. Bivariate analysis showed a significant association between treatment failure and weight loss at first control (OR=1.55), non-decrease in bacillary density at first control (OR=25.5) and treatment discontinuation (OR=20.5). After adjustment, weight loss of 1 kg (adjusted OR=1.92), no decrease in BAAR density (adjusted OR=8.30) and treatment discontinuation (adjusted OR=12.2) remained significantly associated with treatment failure.&#x0D; Conclusion: Active surveillance should be instituted in TB patients with PMT+ who present at first check-up with weight loss, non-decrease in bacillary density on direct examination and/or a notion of treatment discontinuation.

Treatment and management of hypersensitivity reactions developed against anti-tuberculosis drug.

The World Health Organization Global Tuberculosis Report 2021 defines tuberculosis as the second infectious disease that causes sickness and death after COVID 19 and ranks it as the 13th among the global causes of death. However, the prevalence of the patients developing a hypersensitivity reaction against antituberculosis treatment is yet unknown. This study aimed to investigate the prevalence of drug allergy against antituberculosis treatment and the management of such a problem. This is a case--control study. All patients hospitalized in the tuberculosis inpatient service between February 01, 2015 and May 01, 2021 due to hypersensitivity reaction or who developed hypersensitivity during hospitalization were included in the case group. Patients who received inpatient treatment between the same dates and did not develop any drug allergy were included in the control group. The demographic characteristics of the patients, the tuberculosis diagnostic indicator, the type of hypersensitivity reaction that developed, the duration of the manifestation of the reaction and its treatment were evaluated for the purpose of the study. A total of 2677 patients were hospitalized in the tuberculosis inpatient service between the specified dates. Two hundred and ten patients were consulted for drug hypersensitivity reactions in the Allergy Clinic. The prevalence of drug allergy in inpatients was calculated as 7.8%. One hundred and forty-eight patients examined by the authors were included in the study. Seventy-nine of the 148 patients (53.4%) who developed a hypersensitivity reaction were male, the mean age of these patients was 47.20 ± 18.95 years, 89.2% (n = 132) were citizens of the Republic of Turkey, 7.4% (n = 11) of the patients had received tuberculosis treatment before, 16.9% (25) had developed antituberculosis drug resistance and the bacteriological diagnosis was present in 79.7% (118) of the patients. Chi-square test results applied in the allergy group revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P < 0.001), Turkish citizen patients (P = 0.004), in new cases (P = 0.017), in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The results of the logistic regression analysis performed also revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P = 0.006), Turkish citizen patients (P = 0.023), in new cases (P = 0.017) and in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The success of the treatment was higher in the group that developed a hypersensitivity reaction compared to the control group. About 63.5% (94) of the patients examined developed Type I hypersensitivity reactions, whereas 36.7% (53) of the patients examined developed Type IV hypersensitivity reactions. Type I and Type IV reactions were observed simultaneously in a single patient. Considering the prevalence of developing a hypersensitivity reaction, pyrazinamide was determined as the drug inducing the hypersensitivity reaction in 25 (48.1%) patients. This figure was 15 patients (28.2%) for rifampicin, nine patients (17.3%) for isoniazid, and five patients (9.6%) for ethambutol. As a result, even patients who developed Type I or Type IV reactions were able to complete their antituberculous drug regimens with successful desensitization. The risk of developing an allergic reaction in patients who are administered on antituberculosis treatment is common, particularly in the first 2 months of treatment. However, we believe that the compliance of the patients to the antituberculosis treatment has been improved at the end of appropriate management of hypersensitivity reactions and the treatment results in success.

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya

Distribution patterns of drug resistance Mycobacterium tuberculosis among HIV negative and positive tuberculosis patients in Western Kenya

Characteristics of second-line anti-tuberculosis drug resistance and gene mutation of multidrug-resistant Mycobacterium tuberculosis in Ningbo

Objective To analyze the characteristics of second-line anti-tuberculosis (TB) drugs resistance and gene mutation of multidrug-resistant (MDR) Mycobacterium tuberculosis isolated in Ningbo. Methods In 1597 M. tuberculosis isolates collected in the first drug resistance survey in Ningbo between 2018 and 2019, 133 MDR isolates, including 31 isolated from elderly group and 102 isolated from young and middle age group, were used in the study. All the isolates were detected using RD105 deletion-targeted multiplex PCR for Beijing genotype identification. Gene sequencing with PCR was conducted to detect the mutations of rrs, tlyA, eis, gidB, gyrA and gyrB genes. The conventional drug susceptibility test was used to detect the resistances to 5 second-line anti TB drugs (kanamycin, amikacin, capreomycin, ofloxacin, levofloxacin). Results The multidrug resistance rate of M. tuberculosis isolates was 8.33% (133/1597) in Ningbo. The resistance rates of 133 MDR M. tuberculosis isolates to kanamycin, amikacin, capreomycin, ofloxacin and levofloxacin were 7.52% (10/133), 6.01% (8/133), 3.01% (4/133), 30.08% (40/133) and 29.32% (39/133). The rates of Pre-XDR and XDR of 133 MDR M. tuberculosis isolates were 28.57% (38/133) and 6.01% (8/133). The gene mutation rates of rrs, tlyA, eis, gidB, gyrA and gyrB of 133 MDR M. tuberculosis isolates were 6.77% (9/133), 7.52% (10/133), 1.50% (2/133), 3.76% (5/133), 34.59% (46/133) and 3.01% (4/133). There were 2 rrs mutations, 1 tlyA mutation, 2 eis mutations, 2 gidB mutations, 5 gyrA mutations and 4 gyrB mutations. Single base substitution was the main type. Conclusion The resistance of MDR M. tuberculosis to second-line anti-TB drugs was serious in Ningbo, especially the resistance to fluoroquinolone. It is necessary to strengthen the prevention and control of second-line anti TB drugs resistances of MDR M. tuberculosis.

Status of antituberculosis drug resistance in Saudi Arabia 1979-98

All published material on the prevalence of drug-resistant tuberculosis within Saudi Arabia over the period 1979-98 was reviewed. The prevalence of single-drug-resistant tuberculosis ranged from 3.4% to 41% for isoniazid, 0% to 23.4% for rifampicin, 0.7% to 22.7% for streptomycin and 0% to 6.9% for ethambutol. The prevalence of multidrug-resistant tuberculosis (defined by WHO as resistance to two or more first-line antituberculosis drugs) ranged from 1.5% to 44% in different regions. No strong conclusions could be drawn owing to variations in the populations studied, geographical origins, site of Mycobacterium tuberculosis isolation (pulmonary or extrapulmonary) and drug sensitivity testing. However, the need to develop a standardized national policy for surveillance of drug-resistant tuberculosis in Saudi Arabia is clear.