scholarly journals Comparison of Interpretation between Pyrosequencing and Xpert MTB/RIF Assay in Multidrug-Resistant Tuberculosis

2020 ◽  
Vol 52 (4) ◽  
Author(s):  
Linda Choerunnisa ◽  
Ida Parwati ◽  
Coriejati Rita ◽  
Anna Tjandrawati ◽  
Lidya Chaidir
Keyword(s):  
Gene Mutations ◽  
Rpob Gene ◽  
Multidrug Resistant ◽  
Detection Methods ◽  
Isoniazid Resistance ◽  
Resistant Tuberculosis ◽  
Position Detection ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Codon Mutation

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.

HYBRIDIZATION-BASED NUCLEIC ACID AMPLIFICATION TEST TERHADAP CARTRIDGE-BASED NUCLEIC ACID AMPLIFICATION TEST TERKAIT MULTIDRUG-RESISTANT TUBERCULOSIS

2016 ◽  
Vol 21 (3) ◽  
pp. 237
Author(s):  
Ivana Agnes Sulianto ◽  
Ida Parwati ◽  
Nina Tristina ◽  
Agnes Rengga I
Keyword(s):  
Nucleic Acid ◽  
Rpob Gene ◽  
Multidrug Resistant ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
Isoniazid Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Low Sensitivity

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.

scholarly journals Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Second Line ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improper Use ◽  
Mdr Tb

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.

scholarly journals Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis

2015 ◽  
Vol 53 (12) ◽  
pp. 3876-3880 ◽  
Author(s):  
Andrea M. Cabibbe ◽  
Paolo Miotto ◽  
Raquel Moure ◽  
Fernando Alcaide ◽  
Silke Feuerriegel ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Routine Laboratory ◽  
Isoniazid Resistance ◽  
Content Type ◽  
Lab On Chip ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
On Chip ◽  
User Friendly

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.

scholarly journals HYBRIDIZATION-BASED NUCLEIC ACID AMPLIFICATION TEST TERHADAP CARTRIDGE-BASED NUCLEIC ACID AMPLIFICATION TEST TERKAIT MULTIDRUG-RESISTANT TUBERCULOSIS (Hybridization-Based Nucleic Acid Amplification Test towards Catridge-Based Nucleic Acid Amplification Test in Multidrug-Resistant Tuberculosis)

2018 ◽  
Vol 21 (3) ◽  
pp. 237
Author(s):  
Ivana Agnes Sulianto ◽  
Ida Parwati ◽  
Nina Tristina ◽  
Agnes Rengga I
Keyword(s):  
Nucleic Acid ◽  
Multidrug Resistant ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
World Health ◽  
Isoniazid Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Low Sensitivity

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 methoddetermines MDR-TB only from the rifampisin resistance, by detecting mutations that occur on the 81 bp hot-spot region of the rpoBgene. 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 (codon315 katG gene). The aim of this study was to know the validity of the HB-NAAT in detecting MDR-TB using sputum with CB-NAATas the gold standard in a diagnostic study. All of 51 sputums were collected during June 2013 from patients suspected pulmonaryMDR-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-NAATexamination results were 3 MDR-TB, 25 TB non MDR (3 RMR, 6 IMR, 16 susceptible) and 23 non TB. The sensitivity of HB-NAAT was18.75% and specificity 100%. Low sensitivity values may due to the high mutation variations in the samples. So it could not be detectedonly by codons 526 and 531 for rifampisin resistance. For the detection of isoniazid resistance, HB-NAAT have optimal primer at lowconcentrations and it also need more than katG genes to detect isoniazid resistance. Based on this study, it can be conclued, that HBNAAThas low sensitivity but high specificity in the detecting MDR-TB.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

PP581 Catastrophic Costs Of Multidrug-Resistant Tuberculosis: Estimation Based On The Cost Of Treatment In China

2020 ◽  
Vol 36 (S1) ◽  
pp. 43-43
Author(s):  
Lijun Shen ◽  
Shangshang Gu ◽  
Fan Zhang ◽  
Zhao Liu ◽  
Yuehua Liu
Keyword(s):  
Market Price ◽  
Multidrug Resistant ◽  
Policy Support ◽  
World Health ◽  
Chinese Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Affordability ◽  
The Cost

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.

scholarly journals Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar

2019 ◽  
Vol 5 (1) ◽  
pp. 2
Author(s):  
Nang Thu Thu Kyaw ◽  
Aung Sithu ◽  
Srinath Satyanarayana ◽  
Ajay M. V. Kumar ◽  
Saw Thein ◽  
...  
Keyword(s):  
Chest Radiography ◽  
Multidrug Resistant ◽  
Sputum Smear ◽  
Community Based ◽  
Household Contacts ◽  
Resistant Tuberculosis ◽  
Symptom Screening ◽  
Multidrug Resistant Tuberculosis ◽  
Screening Algorithm ◽  
Mdr Tb

Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%–6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%–24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.

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