scholarly journals TB Elimination Requires Discovery and Development of Transformational Agents

2020 ◽  
Vol 10 (7) ◽  
pp. 2605 ◽  
Author(s):  
Christian Lienhardt ◽  
Mario C. Raviglione
Keyword(s):  
Rapid Detection ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
The World ◽  
Health Organization ◽  
Combination Regimens

The World Health Organization (WHO) End Tuberculosis (TB) Strategy has set ambitious targets to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. Given the current rate of TB incidence decline (about 2% per year annually), reaching these targets will require new transformational tools and innovative ways to deliver them. In addition to improved tests for early and rapid detection of TB and universal drug-susceptibility testing, as well as novel vaccines for improved prevention, better, safer, shorter and more efficacious treatments for all forms of TB are needed. Only a handful of new drugs are currently in phase II or III clinical trials, and a few combination regimens are being tested, mainly for drug-resistant TB. In this article, capitalising on an increasingly rich medicine pipeline and taking advantage of new methodological designs with great potential, the main areas where progress is needed for a transformational improvement of treatment of all forms of TB are described.

scholarly journals Validation of Bedaquiline Phenotypic Drug Susceptibility Testing Methods and Breakpoints: a Multilaboratory, Multicountry Study

2020 ◽  
Vol 58 (4) ◽  
Author(s):  
Koné Kaniga ◽  
Akio Aono ◽  
Emanuele Borroni ◽  
Daniela Maria Cirillo ◽  
Christel Desmaretz ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Improve Patient Care ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Error Rates ◽  
World Health ◽  
Health Concern ◽  
Content Type ◽  
Indicator Tube ◽  
Health Organization

ABSTRACT Drug-resistant tuberculosis persists as a major public health concern. Alongside efficacious treatments, validated and standardized drug susceptibility testing (DST) is required to improve patient care. This multicountry, multilaboratory external quality assessment (EQA) study aimed to validate the sensitivity, specificity, and reproducibility of provisional bedaquiline MIC breakpoints and World Health Organization interim critical concentrations (CCs) for categorizing clinical Mycobacterium tuberculosis isolates as susceptible/resistant to the drug. Three methods were used: Middlebrook 7H11 agar proportion (AP) assay, broth microdilution (BMD) assay, and mycobacterial growth indicator tube (MGIT) assay. Each of the five laboratories tested the 40-isolate (20 unique isolates, duplicated) EQA panel at three time points. The study validated the sensitivity and specificity of a bedaquiline MIC susceptibility breakpoint of 0.12 μg/ml for the BMD method and WHO interim CCs of 1 μg/ml for MGIT and 0.25 μg/ml for the 7H11 AP methods. Categorical agreements between observed and expected results and sensitivities/specificities for correctly identifying an isolate as susceptible/resistant were highest at the 0.25, 0.12, and 1 μg/ml bedaquiline concentrations for the AP method, BMD (frozen or dry plates), and MGIT960, respectively. At these concentrations, the very major error rates for erroneously categorizing an isolate as susceptible when it was resistant were the lowest and within CLSI guidelines. The most highly reproducible bedaquiline DST methods were MGIT960 and BMD using dry plates. These findings validate the use of standardized DST methodologies and interpretative criteria to facilitate routine phenotypic bedaquiline DST and to monitor the emergence of bedaquiline resistance.

scholarly journals Direct detection of resistance to fluoroquinolones/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kamal Singh ◽  
Richa Kumari ◽  
Smita Gupta ◽  
Rajneesh Tripathi ◽  
Anjali Srivastava ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Direct Detection ◽  
Uttar Pradesh ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
High Rate ◽  
World Health ◽  
Second Line ◽  
Indicator Tube ◽  
Health Organization

Abstract Background According to World Health Organization (WHO), drug-resistant tuberculosis (DR-TB) is a major contributor to antimicrobial resistance globally and continues to be a public health threat. Annually, about half a million people fall ill with DR-TB globally. The gradual increase in resistance to fluoroquinolones (FQs) and second-line injectable drugs (SLIDs), poses a serious threat to effective TB control and adequate patient management. Therefore, WHO suggests the use of GenoType MTBDRsl v.2.0 assay for detection of multiple mutations associated with FQs and SLIDs. Hence, the study was conducted to determine the prevalence of resistance to FQs and SLIDs by comparing direct GenoType MTBDRsl v.2.0 assay with phenotypic drug susceptibility testing (DST). Methods The study was conducted on 1320 smear positive sputum samples from a total of 2536 RR-TB, confirmed by GeneXpert MTB/RIF. The smear positive specimens were decontaminated, and DNA extraction was performed. Furthermore, the extracted DNA was used for GenoType MTBDRsl v.2.0 assay. While 20% of the decontaminated specimens were inoculated in Mycobacterium growth indicator tube (MGIT) for drug susceptibility testing (DST). Results Out of 1320 smear positive sputum samples, 1178 were identified as Mycobacterium tuberculosis complex (MTBC) and remaining were negative by GenoType MTBDRsl v.2.0 assay. Of the 1178 MTBC positive, 26.6% were sensitive to both FQs and SLIDs, whereas 57.3% were only FQs resistant and 15.9% were resistant to both FQs and SLIDs. Further DST of 225 isolates by liquid culture showed that 17% were sensitive to both FQs and SLIDs, 61.3% were only FQs resistant and 21.3% were resistant to both. The specificity for FQs and SLIDs was 92.31% and 100% whereas sensitivity was 100% respectively by GenoType MTBDRsl v.2.0 assay in direct sputum samples. Conclusions Our study clearly suggests that GenoType MTBDRsl v.2.0 assay is a reliable test for the rapid detection of resistance to second-line drugs after confirmation by GeneXpert MTB/RIF assay for RR-TB. Though, high rate FQ (ofloxacin) resistance was seen in our setting, moxifloxacin could be used as treatment option owing to very low resistance.

scholarly journals Testing Susceptibility of M. tuberculosis to Second Line Anti-Tuberculosis Drugs Using the XDR Test in Clinical Trials and International Professional Testing Cycles

2021 ◽  
Vol 99 (8) ◽  
pp. 13-20
Author(s):  
L. V. Domotenko ◽  
T. P. Morozova ◽  
M. V. Khramov ◽  
А. P. Shepelin
Keyword(s):  
Clinical Trials ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
World Health ◽  
Clinical Samples ◽  
Second Line ◽  
Tuberculosis Patients ◽  
Testing Susceptibility ◽  
Health Organization

The objective of the study: to evaluate the commercial XDR test for susceptibility testing of M. tuberculosis to second line anti-tuberculosis drugs in clinical trials and as part of annual professional testing cycles coordinated by the World Health Organization (WHO).Subjects and Methods. Cultures of M. tuberculosis (n = 90) freshly isolated on egg media from clinical samples collected in tuberculosis patients were tested using the Bactec MGIT 960 system and the XDR test under identical conditions. Well-studied strains of M. tuberculosis (n = 216) obtained from the WHO supranational laboratories were repeatedly cultured on Middlebrook 7H10 medium before the study. The drug susceptibility of the cultures was assessed using the XDR test by the nitrate reductase method.Results. A high concurrence (96.7-100%) of the results was shown when testing susceptibility of 90 M. tuberculosis isolates to kanamycin, amikacin, capreomycin and ofloxacin using the XDR test and the Bactec MGIT 960 system with comparable test periods. The use of the XDR test for drug susceptibility testing of 216 M. tuberculosis strains in eleven annual professional testing cycles coordinated by the WHO supranational laboratories provided the results consistent with the consensus one for kanamycin, capreomycin, ofloxacin and amikacin in 98.6, 99.4, 99.4, and 99.0% of cases, respectively. For moxifloxacin and levofloxacin additionally incorporated to the XDR test, completely identical results were obtained.

scholarly journals Clinical Management of Drug-Resistant Tuberculosis in Resource Constrained Settings

2013 ◽  
Vol 5 ◽  
pp. CMT.S6560
Author(s):  
Domingo Palmero ◽  
Viviana Ritacco
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
Drug Resistant ◽  
Resource Constrained ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Repurposed Drugs ◽  
Culture Identification

Drug-resistant forms of tuberculosis (TB), particularly multi- and extensively drug-resistant TB, represent an important obstacle to global control of the disease. Recently, new drugs, repurposed drugs, and new drug combinations have been evaluated, with a number showing promise for the treatment of drug-resistant TB. Additionally, a range of methods for accelerating mycobacterial culture, identification, and drug susceptibility testing have been developed, and several in-house and commercial genotyping methods for speeding drug resistance detection have become available. Despite these significant achievements in drug development and diagnostics, drug-resistant TB continues to be difficult to diagnose and treat. Significant international efforts are still needed, especially in the field of clinical and operational research, to translate these encouraging developments into effective patient cure and make them readily available to resource-constrained settings, where they are most needed.

scholarly journals Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

2021 ◽  
Author(s):  
◽  
Joshua J Carter
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Quantitative Measurement ◽  
Target Gene ◽  
Microtiter Plate ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
World Health ◽  
Genetic Determinants ◽  
Microtiter Plate Assay ◽  
Health Organization

AbstractThe World Health Organization goal of universal drug susceptibility testing for patients with tuberculosis is most likely to be achieved through molecular diagnostics; however, to date these have focused largely on first-line drugs, and always on predicting binary susceptibilities. Here, we used whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration in 15,211 Mycobacterium tuberculosis patient isolates from 27 countries across five continents.This work identifies 449 unique MIC-elevating genetic determinants across thirteen drugs, as well as 91 mutations resulting in hypersensitivity for eleven drugs. Our results provide a guide for further implementation of personalized medicine for the treatment of tuberculosis using genetics-based diagnostics and can serve as a training set for novel approaches to predict drug resistance.

Bioactive Natural Medicinal Plants in South Indian Western Ghats and Their Pharmacological Importance

2020 ◽  
Vol 6 (2) ◽  
pp. 62-69
Author(s):  
M. Tamizharasi ◽  
R. Rajila ◽  
D. Beula Shiny ◽  
J. Vijila Jasmin ◽  
T. Kumaran
Keyword(s):  
Medicinal Plants ◽  
Western Ghats ◽  
New Drugs ◽  
World Health ◽  
Plant Resources ◽  
Medical Products ◽  
Primary Health ◽  
South Indian ◽  
The World ◽  
Health Organization

Awareness of traditional knowledge and medicinal plants can play a key role in the utilization and discovery of natural plant resources. Plants became the basis of medicine system throughout the world for thousands of years and continue to provide mankind with new remedies. Researchers generally agree that natural products from plants and other organisms have been the most consistently successful source for ideas for new drugs. The world health organization estimates that 80% of the population living in the developing countries relies exclusively on traditional medicine for their primary health care. More than half of the world's population still relies entirely on plants for medicines, and plants supply the active ingredients of most traditional medical products. The review shows the south Indian medicinal plant products has been used by people to treat various health ailments.

scholarly journals Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

2019 ◽  
Vol 147 ◽  
Author(s):  
R. S. Salvato ◽  
S. Schiefelbein ◽  
R. B. Barcellos ◽  
B. M. Praetzel ◽  
I. S. Anusca ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Characterisation ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
High Burden ◽  
Brics Countries ◽  
Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

scholarly journals GeneXpert MTB/RIF Assay for Rapid Identification of Mycobacterium Tuberculosis and Rifampicin Resistance Directly from Sputum Sample

2017 ◽  
Vol 7 (2) ◽  
pp. 86-89 ◽  
Author(s):  
Nourjahan Laskar ◽  
Md Akram Hossain ◽  
Jannatul Fardows ◽  
Mominur Rahman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sputum Sample ◽  
Rapid Identification ◽  
Rapid Diagnosis ◽  
World Health ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
The World ◽  
Health Organization

Background: The World Health Organization has endorsed the use of molecular methods for the detection of tuberculosis (TB) and drug resistant TB as a rapid method. In Bangladesh, the Xpert MTB/RIF assay has been implemented into reference laboratories for diagnosis of TB and also MDR TB.Objective: Drug resistant tuberculosis has long been a common problem prevailing in our country. The present study focused on the rapid identification of Mycobacterium tuberculosis as well as drug resistance.Materials and Methods: Sputum samples from a total of 107 cases, assumed as multi-drug resistance tuberculosis, were studied through GeneXpert assay.Results: Out of 107 cases, 91 (85.05%) were detected having M. tuberculosis ? 64 (59.81%) were rifampicin sensitive and 27 (25.23%) were rifampicin resistant. The sensitivity and specificity of the GeneXpert are 87.64% and 75% respectively.Conclusion: GeneXpert assay can be considered for the rapid diagnosis of drug resistant tuberculosis.J Enam Med Col 2017; 7(2): 86-89

scholarly journals Susceptibility Testing of Extensively Drug-Resistant and Pre-Extensively Drug-Resistant Mycobacterium tuberculosis against Levofloxacin, Linezolid, and Amoxicillin-Clavulanate

2013 ◽  
Vol 57 (6) ◽  
pp. 2522-2525 ◽  
Author(s):  
Imran Ahmed ◽  
Kauser Jabeen ◽  
Raunaq Inayat ◽  
Rumina Hasan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Critical Concentration ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Fluoroquinolone Resistance ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Amoxicillin Clavulanate

ABSTRACTPakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR)Mycobacterium tuberculosisagainst LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC.M. tuberculosisH37Rv was used as a control strain. A total of 102M. tuberculosisisolates (XDR,n= 59; pre-XDR,n= 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases.

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