scholarly journals First insight into the genotype and molecular epidemiology of MDR-TB isolates from Chongqing Municipality of China using 24-loci MIRU-VNTR technique

2019 ◽  
Author(s):  
Lei Xu ◽  
Yan Hu ◽  
Tongxin Li ◽  
Chun Yang ◽  
Yonglin He ◽  
...  
Keyword(s):  
Variable Number Tandem Repeat ◽  
Melting Curve ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Beijing Genotype ◽  
Molecular Characteristics ◽  
Chongqing Municipality ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
High Discriminatory Power

Abstract Background: Multidrug-resistant tuberculosis (MDR-TB) has become a great threat to TB control around the world. In 2017, there were 889,000 new tuberculosis cases in China, and 31.1% were MDR/RR-TB (TB resistant to rifampicin). This study aims to explore the the molecular characteristics and factors associated with infection among different genotype MDR strains in Chongqing, China. Methods: All the 230 MDR-TB isolates were genotyped using 24-loci mycobacterial interspersed repetitive unite variable number tandem repeat (MIRU-VNTR) method and multiplex real-time PCR melting curve assay of Rv2952 gene and mutT2 gene. Polymorphism and clustering analysis of each locus was carried out by BioNumerics Version 5.0. Results: By genotyping, 83.0% (191/230) of the MDR-TB isolates were Beijing strains, among which 41.9% from the ancient Beijing genotype and 58.1% from the modern Beijing genotype. Based on 24-loci, the 230 MDR isolates were classified into 208 genotypes, among which 38 isolates belonged to 16 clusters. The clustering rate was 16.5%. The percentages of SM-resistant and EMB-resistant in Beijing genotype were significantly higher than those in non-Beijing genotype (P < 0.01). The Beijing genotype had a significantly high risk to be clustered than non-Beijing genotype (p < 0.01). The percentages of SM-resistant isolates in clustered group were significantly higher than non-clustered group (P < 0.01). According to 24-loci, the HGDI was 0.9988, and five loci (Qub11b, Qub26, Mtub21, MIRU26, Mtub04) have high discriminatory power (HGDI > 0.6), while 7 loci (MIRU4, MIRU23, Mtub34, MIRU20, Mtub29, MIRU2, MIRU24) showed negligible diversity (HGDI < 0.1). The percentage of clustered rate showed no difference between 24-loci and 15-loci (p = 0.19). Conclusion: Among MDR isolates in Chongqing China, Beijing genotype is more likely to be drug resistant and clustered, and SM-resistant isolates are more likely to be clustered that may related to the MDR epidemic. Although 24-loci had a high resolution of genotype, some new loci should be found to replace the poor diversity loci in 24-loci and additional analysis of specific sublineage of Beijing genotype is needed in order to better understand the relations between the molecular characteristics of strains and MDR-TB epidemic.

scholarly journals Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China

2016 ◽  
Vol 60 (5) ◽  
pp. 2807-2812 ◽  
Author(s):  
Qin-jing Li ◽  
Wei-wei Jiao ◽  
Qing-qin Yin ◽  
Fang Xu ◽  
Jie-qiong Li ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Variable Number Tandem Repeat ◽  
Northern China ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Beijing Genotype ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Rifampin Resistance

ABSTRACTMycobacterium tuberculosiscan acquire resistance to rifampin (RIF) through mutations in therpoBgene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in therpoAorrpoCgene. This study aimed to identifyrpoAandrpoCmutations in clinicalM. tuberculosisisolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found inrpoAorrpoCof the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in therpoA(n= 6) orrpoC(n= 83) gene. The proportion ofrpoCmutations was significantly higher in new cases (P= 0.023) and in strains with therpoBS531L mutation (P< 0.001). In addition, multidrug-resistant (MDR) strains withrpoCmutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat clustering (P= 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDRM. tuberculosisstrains.

scholarly journals Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

2020 ◽  
Author(s):  
Janisara Rudeeaneksin ◽  
Benjawan Phetsuksiri ◽  
Chie Nakajima ◽  
Supranee Bunchoo ◽  
Krairerk Suthum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Drug Resistant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

scholarly journals Tuberculous Spondylitis in Russia and Prominent Role of Multidrug-Resistant Clone Mycobacterium tuberculosis Beijing B0/W148

2015 ◽  
Vol 59 (4) ◽  
pp. 2349-2357 ◽  
Author(s):  
Anna Vyazovaya ◽  
Igor Mokrousov ◽  
Natalia Solovieva ◽  
Alexander Mushkin ◽  
Olga Manicheva ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Spinal Tuberculosis ◽  
Variable Number Tandem Repeat ◽  
Molecular Study ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Beijing Genotype ◽  
Tuberculous Spondylitis ◽  
Content Type

ABSTRACTExtrapulmonary and, in particular, spinal tuberculosis (TB) constitutes a minor but significant part of the total TB incidence. In spite of this, almost no studies on the genetic diversity and drug resistance ofMycobacterium tuberculosisisolates from spinal TB patients have been published to date. Here, we report results of the first Russian and globally largest molecular study ofM. tuberculosisisolates recovered from patients with tuberculous spondylitis (TBS). The majority of 107 isolates were assigned to the Beijing genotype (n= 80); the other main families were T (n= 11), Ural (n= 7), and LAM (n= 4). Multidrug resistance (MDR) was more frequently found among Beijing (90.5%) and, intriguingly, Ural (71.4%) isolates than other genotypes (5%;P< 0.001). The extremely drug-resistant (XDR) phenotype was exclusively found in the Beijing isolates (n= 7). A notable prevalence of therpoB531andkatG315mutations in Beijing strains that were similarly high in both TBS (this study) and published pulmonary TB (PTB) samples from Russia shows that TBS and PTB Beijing strains follow the same paradigm of acquisition of rifampin (RIF) and isoniazid (INH) resistance. The 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) subtyping of 80 Beijing isolates further discriminated them into 24 types (Hunter Gaston index [HGI] = 0.83); types 100-32 and 94-32 represented the largest groups. A genotype of Russian successful clone B0/W148 was identified in 30 of 80 Beijing isolates. In conclusion, this study highlighted a crucial impact of the Beijing genotype and the especially prominent role of its MDR-associated successful clone B0/W148 cluster in the development of spinal MDR-TB in Russian patients.

scholarly journals MOLECULAR EPIDEMIOLOGY OF MULTIDRUG RESISTANT TUBERCULOSIS IN MONGOLIA AND EASTERN SIBERIA: TWO INDEPENDENT DISSEMINATION PROCESSES FOR DOMINANT STRAINS

2019 ◽  
Author(s):  
S. Zhdanova ◽  
M. Badleeva ◽  
O. Ogarkov ◽  
E. Orlova
Keyword(s):  
Hiv Infection ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Eastern Siberia ◽  
Cross Border ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Wide Range ◽  
Mdr Tb ◽  
The Cross

Mongolia and Russia are among the countries with the high tuberculosis (TB) burden. The prevalence of tuberculosis, including multidrug-resistant tuberculosis (MDR), in Eastern Siberia bordering Mongolia is significantly higher than that of in the European part of Russia. In addition, unlike Mongolia, Eastern Siberia is characterized by a high prevalence of HIV infection. The cross-border spread of socially significant infections in these countries seems to be occur due to their wide-range cooperation and cultural exchange. Whereas the HIV infection has no epidemiological significance for Mongolia at the moment, tuberculosis, however, on both sides of the border has a similar prevalence. The aim was to evaluate the cross-border MDR M. tuberculosis distribution in Mongolia and Eastern Siberia by using molecular genetic data.Materials and methods: A total of 1045 M. tuberculosis strains isolated in Mongolia (291) and the three regions of Eastern Siberia (754) were studied by using the MIRU-VNTR - 24 loci genotyping. The CC2/W148 and CC1 subtype was identified by the specific deletion in the kdpD gene and SNP in the pks17 gene at position 1887060, respectively.Phylogenetic analysis of MIRU-VNTR patterns was carried out by generating UPGMA tree and maximum likelihood tree. Results. The Beijing genotype was found in 75.3% (219/291) and 69.0% (520/754) from Mongolian and East Siberian collect ion, respectively. Common minor genotypes were LAM (11.0% and 15.1%), T (10.3% and 4.5%), Haarlem (1.4% and 2.4%) found in Mongolia and Eastern Siberia, respectively. The genotype S (1.3%) and Ural (5.0%) was found solely in the Russia-derived samples. The main epidemic Beijing subtypes in each country belonged to different clonal complexes (CC): the majority of Mongolian Beijing strains displayed profiles 342-32, 3819-32, 1773-32 MLVA types and belonged to the CC4 subtype; Russian Beijing strains mainly belonged to the CC1 (43.7% - 227/520) and CC2/W148 (34.8% - 181/520) subtypes.The MDR level and distribution patterns differed significantly between Mongolia and Eastern Siberia. Modeling of Beijing strain expansion evidences about extremely subtle contribution of the M. tuberculosis cross-border transmission between Mongolia and Russia. The phylogenetic reconstruction of Beijing CC4 subtype evolution in Mongolia suggests that its distribution is primarily associated with China and other countries of the West Pacific region. Three main phylogenetic branches of CC4 subtype were traced, which probably spread throughout Mongolia in the 11-12th centuries. It may be assumed that spread of the epidemic Beijing CC4 subtype might occur in two stages: early period – emergence of ancestral CC4 variants in Mongolia or their introduction from China (they are homologous to the strains preserved in the Chinese population); later period – dissemination due to the active exchange of M. tuberculosis with countries of Southeast Asia, but not Russia.Conclusion. Using MIRU-VNTR 24 genotyping as well as classification according to specific single nucleotide polymorphisms specific to certain Beijing subtypes, it allowed to describe separate patterns of the epidemic variants spread in Mongolia and Russia. It has been demonstrated that emergence and spread of MDR-TB in Mongolia is entirely iatrogenic in nature, while the epidemic subtypes of the Beijing genotype (subtypes CC1 and CC2 / W148) contribute markedly into the MDR-TB spread in Eastern Siberia.

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.

scholarly journals The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Pulse Field ◽  
Virulence Determinants ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

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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