scholarly journals The impact of combined gene mutations in inhA and ahpC genes on high levels of isoniazid resistance amongst katG non-315 in multidrug-resistant tuberculosis isolates from China

2018 ◽  
Vol 7 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Liguo Liu ◽  
Fengting Jiang ◽  
Lihong Chen ◽  
Bing Zhao ◽  
Jie Dong ◽  
...  
2020 ◽  
Vol 52 (4) ◽  
Author(s):  
Linda Choerunnisa ◽  
Ida Parwati ◽  
Coriejati Rita ◽  
Anna Tjandrawati ◽  
Lidya Chaidir

Indonesia is one of the countries with the highest multidrug-resistant tuberculosis cases in the world. Rapid molecular test using the Xpert MTB/RIF assay is one of the detection methods for MDR-TB. Early detection of MDR-TB is crucial for early initiation of treatment. However, Xpert MTB/RIF assay only detects the rpoB gene mutations associated with Rifampicin resistance. Recently, WHO recommends the use of Pyrosequencing, a DNA sequencing method that can detect not only the rpoB gene but also katG and/or inhA gene mutations associated with Isoniazid resistance. The aims of this study were to compare the interpretation between the two methods and to determine the differences in codon mutation position detection of the rpoB gene and mutation detection of the katG and/or inhA gene. This was a cross-sectional comparative observational study on patients ≥18 years old interpreted as RR-TB patients based on Xpert MTB/RIF assay results who had not received MDR-TB drugs at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Results showed there were 40 Rifampicin-resistant TB subjects interpreted by Xpert MTB/RIF assay while Pyrosequencing interpreted 30 MDR-TB, 9 RR-TB and one Isoniazid-resistant TB subjects in January - February 2020. The detection of rpoB gene codon mutation position between Xpert MTB/RIF assay and Pyrosequencing methods was not significantly different (p=0.389). Pyrosequencing had detected 27 katG gene mutations, 3 inhA gene mutations, one katG and inhA gene mutation. To conclude, Pyrosequencing can be used for accurate detection of Rifampicin and Isoniazid resistance in MDR-TB.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.


Author(s):  
Ivana Agnes Sulianto ◽  
Ida Parwati ◽  
Nina Tristina ◽  
Agnes Rengga I

Indonesia has high burden of multidrug-resistant tuberculosis (MDR-TB). Cartridge-based nucleic acid amplification test (CB-NAAT), which is recommended as a diagnostic method of MDR-TB by World Health Organization, is faster in achieving the result. This method determines MDR-TB only from the rifampisin resistance, by detecting mutations that occur on the 81 bp hot-spot region of the rpoB gene. The isoniazid resistance is not included in the determination of MDR-TB by this method. Hybridization-based NAAT (HB-NAAT) detects MDR-TB not only from the rifampisin resistance (codon 526 and 531 rpoB gene), but also from the isoniazid resistance (codon 315 katG gene). The aim of this study was to know the validity of the HB-NAAT in detecting MDR-TB using sputum with CB-NAAT as the gold standard in a diagnostic study. All of 51 sputums were collected during June 2013 from patients suspected pulmonary MDR-TB at Dr. Hasan Sadikin General Hospital. The result of CB-NAAT were 16 MDR-TB, 12 TB non MDR, and 23 non TB. HB-NAAT examination results were 3 MDR-TB, 25 TB non MDR (3 RMR, 6 IMR, 16 susceptible) and 23 non TB. The sensitivity of HB-NAAT was 18.75% and specificity 100%. Low sensitivity values may due to the high mutation variations in the samples. So it could not be detected only by codons 526 and 531 for rifampisin resistance. For the detection of isoniazid resistance, HB-NAAT have optimal primer at low concentrations and it also need more than katG genes to detect isoniazid resistance. Based on this study, it can be conclued, that HBNAAT has low sensitivity but high specificity in the detecting MDR-TB.


Author(s):  
N.A. Lytvynenko ◽  
Yu.O. Senko ◽  
L.M. Protsyk ◽  
V.V. Davydenko ◽  
S.P. Korotchenko ◽  
...  

Tuberculosis is a severe infectious disease that negatively affects not only the physical condition of patients, but also the psychological condition of patients. The first thing — the shock of the first diagnosis of tuberculosis for the patient. The second thing — when the patient realizes that he must be treated for an unusually long time. Objective — to learn the impact of providing psychological support for the patients with tuberculosis in a phthisiatric hospital in the form of individual counseling and group classes for patients. Materials and methods. A prospective surgical study was provided to establish the level of knowledge, level of adherence to treatment of patients with tuberculosis and the degree of violation of their psycho-emotional state at the beginning of treatment, and individual counseling and group classes for patients. The study included 335 patients with multidrug-resistant pulmonary tuberculosis, who received treatment at the clinic of the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine on short-term and individualized regimens of antimycobacterial therapy in the framework of scientific developments. Patients received questionnaires before treatment and before discharge, counseling on tuberculosis and their psychological state, various group classes. Results and discussion. A comprehensive approach of treatment using different methods of psychological support allowed increasing the level of adherence to treatment by 32% in the group of patients who received a group classes, compared with those patients who didn’t; reduce the level of stigma by 40.5%, halve the severity anxiety disorders. Conclusions. Comprehensive psychological support should be a mandatory component in the treatment of patients with multidrug-resistant tuberculosis, which can significantly reduce stigma, improve the psychological state of patients and their adaptation in society.


BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e034821 ◽  
Author(s):  
Kefyalew Addis Alene ◽  
Akilew Awoke Adane ◽  
Alemken Jegnie

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes.Methods and analysisThis systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies.Ethics and disseminationAs it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.


2015 ◽  
Vol 53 (12) ◽  
pp. 3876-3880 ◽  
Author(s):  
Andrea M. Cabibbe ◽  
Paolo Miotto ◽  
Raquel Moure ◽  
Fernando Alcaide ◽  
Silke Feuerriegel ◽  
...  

We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplusassay forMycobacterium tuberculosiscomplex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use.


2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
M. Maliyoni ◽  
P. M. M. Mwamtobe ◽  
S. D. Hove-Musekwa ◽  
J. M. Tchuenche

Tuberculosis, an airborne disease affecting almost a third of the world’s population remains one of the major public health burdens globally, and the resurgence of multidrug-resistant tuberculosis in some parts of sub-Saharan Africa calls for concern. To gain insight into its qualitative dynamics at the population level, mathematical modeling which require as inputs key demographic and epidemiological information can fill in gaps where field and lab data are not readily available. A deterministic model for the transmission dynamics of multi-drug resistant tuberculosis to assess the impact of diagnosis, treatment, and health education is formulated. The model assumes that exposed individuals develop active tuberculosis due to endogenous activation and exogenous re-infection. Treatment is offered to all infected individuals except those latently infected with multi-drug resistant tuberculosis. Qualitative analysis using the theory of dynamical systems shows that, in addition to the disease-free equilibrium, there exists a unique dominant locally asymptotically stable equilibrium corresponding to each strain. Numerical simulations suggest that, at the current level of control strategies (with Malawi as a case study), the drug-sensitive tuberculosis can be completely eliminated from the population, thereby reducing multi-drug resistant tuberculosis.


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