Identification, Synthesis, Isolation and Spectral Characterization of Multidrug-Resistant Tuberculosis (MDR-TB) Related Substances

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.

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Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolates from China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01792-13 ◽

2014 ◽

Vol 58 (4) ◽

pp. 1997-2005 ◽

Cited By ~ 18

Author(s):

Li-Li Zhao ◽

Yan Chen ◽

Hai-Can Liu ◽

Qiang Xia ◽

Xiao-Cui Wu ◽

...

Keyword(s):

Molecular Characterization ◽

Multidrug Resistant ◽

Diagnostic Methods ◽

Molecular Diagnostic ◽

Beijing Family ◽

Phenotypic Data ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

ABSTRACTTo investigate the molecular characterization of multidrug-resistant tuberculosis (MDR-TB) isolates from China and the association of specific mutations conferring drug resistance with strains of different genotypes, we performed spoligotyping and sequenced nine loci (katG,inhA, theoxyR-ahpCintergenic region,rpoB,tlyA,eis,rrs,gyrA, andgyrB) for 128 MDR-TB isolates. Our results showed that 108 isolates (84.4%) were Beijing family strains, 64 (59.3%) of which were identified as modern Beijing strains. Compared with the phenotypic data, the sensitivity and specificity of DNA sequencing were 89.1% and 100.0%, respectively, for isoniazid (INH) resistance, 93.8% and 100.0% for rifampin (RIF) resistance, 60.0% and 99.4% for capreomycin (CAP) resistance, 84.6% and 99.4% for kanamycin (KAN) resistance, and 90.0% and 100.0% for ofloxacin (OFX) resistance. The most prevalent mutations among the MDR-TB isolates werekatG315,inhA15,rpoB531, -526, and -516,rrs1401,eis-10, andgyrA94, -90, and -91. Furthermore, there was no association between specific resistance-conferring mutations and the strain genotype. These findings will be helpful for the establishment of rapid molecular diagnostic methods to be implemented in China.

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Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

Antibiotics ◽

10.3390/antibiotics10101169 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1169

Author(s):

Precious Bwalya ◽

Tomoyuki Yamaguchi ◽

Eddie Samuneti Solo ◽

Joseph Yamweka Chizimu ◽

Grace Mbulo ◽

...

Keyword(s):

Multidrug Resistant ◽

Streptomycin Resistance ◽

University Teaching ◽

Reference Laboratory ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The University

Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.

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Prevalence of Multidrug-Resistant Tuberculosis Using Phenotypic Drug Susceptibility Testing and GeneXpert MTB/RIF with Characterization of Non-tuberculous Mycobacteria Using MALDI-TOF

10.51429/ejmm30319 ◽

2021 ◽

Vol 30 (3) ◽

pp. 143-151

Author(s):

Noha S. Soliman ◽

Sahar M. Khairat ◽

Mohamed Abdullah ◽

Yasmin Adel El-Mahdy

Keyword(s):

Susceptibility Testing ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Health Concern ◽

Maldi Tof ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Background: Multidrug-resistant tuberculosis (MDR-TB) and infections by nontuberculous mycobacteria (NTM) are diseases of major public health concern. Objective: The aim of the present work is to study the prevalence and patterns of MDRTB as well as the characterization of isolated NTM species. Methodology: All samples (1069) were subjected to smear microscopy, culture on Lowenstein-Jensen (LJ) media, and phenotypic drug susceptibility testing (DST) of MTB to isoniazid (INH), rifampin (RF), streptomycin (S), and ethambutol (E). GeneXpert was used for direct detection of MTB and RF resistance. Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS) was utilized for characterizing isolated NTM species. Results: M.tuberculosis (MTB) was isolated at a rate of 95.3% (1019/1069). MDR-TB was detected at rate of 7.16% with significant patterns for INH + RF + S + E (46.5%) and INR + RF (24.6%) (P-value <0.001). RF resistance was detected at a rate of 27.2% by GeneXpert. Seven NTM species (0.6%) were isolated in culture of which M.porcinum and M.fortuitum had confident identification by MALDI-TOF (score ≥1.8). Conclusion: MDR-TB rate was found to be 7.16% with significant dominance for INH + RF + S + E and INR + RF resistance patterns, while NTM rate was 0.6%.

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Faculty Opinions recommendation of Development and evaluation of a pilot nurse case management model to address multidrug-resistant tuberculosis (MDR-TB) and HIV in South Africa.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725239549.793504303 ◽

2015 ◽

Author(s):

Rannakoe Lehloenya

Keyword(s):

South Africa ◽

Case Management ◽

Multidrug Resistant ◽

Management Model ◽

Nurse Case Management ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

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Multidrug-Resistant Tuberculosis (MDR-TB) Control Activities in Kano State, North West Nigeria: Progress so Far

TEXILA INTERNATIONAL JOURNAL OF PUBLIC HEALTH ◽

10.21522/tijph.2013.se.19.02.art002 ◽

2019 ◽

pp. 6-12

Author(s):

Musa K. Bawa

Keyword(s):

Multidrug Resistant ◽

North West ◽

Tb Control ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

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

BMC Medicine ◽

10.1186/s12916-021-01932-7 ◽

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.

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

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320002032 ◽

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.

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

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010002 ◽

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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