scholarly journals Mycobacterium Tuberculosis Strain Lineage in Mixed Tribal Population Across India and Andaman Nicobar Island

2021 ◽  
Author(s):  
Azger Dusthackeer V. N. ◽  
Azger Dusthackeer V. N. ◽  
Ashok Kumar ◽  
Kannappan Kannappan Sucharitha ◽  
S. Shivakumar ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Small Sample ◽  
Clinical Isolates ◽  
Nicobar Island ◽  
Tribal Population ◽  
Indian States ◽  
Mdr Tb

Abstract In India, the tribal population constitutes almost 8.6% of the nation’s total population. This study attempts to provide information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in 10 Indian states and Andaman & Nicobar (A&N) Island. Clinical isolates were received from 66 villages (10 states and island). A total of 78 M. tuberculosis clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed. The major M. tuberculosis strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant tuberculosis (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.

Linezolid resistance among multidrug-resistant Mycobacterium tuberculosis clinical isolates in Iran

2021 ◽  
Author(s):  
Azar Dokht Khosravi ◽  
Mohammad Reza Tabandeh ◽  
Fatemeh Shahi ◽  
Shokrollah Salmanzadeh
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Microdilution Method ◽  
Linezolid Resistance ◽  
Main Challenge ◽  
Broth Microdilution Method ◽  
Mdr Tb

AbstractThe management of multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) presents a main challenge and the drug options for treating these infections are very limited. Linezolid (LNZ) has recently been approved for the treatment of MDR and XDR-TB. But, there are narrow data on genotypic and phenotypic LNZ resistance in clinical isolates. So, we aimed to determine the prevalence of LNZ resistance and to identify the mutations associated with LNZ resistance among clinical MDR-TB isolates. The minimum inhibitory concentration (MIC) values of LNZ for 22 MDR-TB isolates were determined by broth microdilution method. All MDR-TB isolates were sequenced in the rrl and rplC genes conferring LNZ resistance. LNZ resistance was found in 3 (13.6%) of 22 MDR-TB isolates. The MICs of LNZ were 8 μg/mL for two isolates and 16 μg/mL for one isolate. The 421 (A/G) and 449 (T/A) mutations in rplC gene were detected in one of the LNZ-resistant isolates. There was no mutation in rrl gene. The results reveal that the prevalence of LNZ-resistant isolates is 13.6% among MDR-TB isolates and drug susceptibility testing (DST) against LNZ is useful in the management of complicated and drug-resistant cases. However, further studies could identify other possible genetic mechanism of resistance in TB.

scholarly journals Rapid Molecular Diagnosis of Tuberculosis and Its Resistance to Rifampicin and Isoniazid with Automated MDR/MTB ELITe MGB® Assay

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 797
Author(s):  
Vichita Ok ◽  
Alexandra Aubry ◽  
Florence Morel ◽  
Isabelle Bonnet ◽  
Jérôme Robert ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Samples ◽  
Great Promise ◽  
Routine Practice ◽  
Pcr Assay ◽  
Perfect Agreement ◽  
Mdr Tb ◽  
Good Agreement

The MDR/MTB ELITe MGB® kit (ELITech) carried on the ELITe InGenius® platform is a new real-time PCR assay allowing automated extraction and detection of DNA of the Mycobacterium tuberculosis complex (MTB) and mutations in the rpoB and katG genes and inhA promoter region (pro-inhA) associated to resistance to rifampicin and isoniazid, the two markers of multidrug-resistant TB (MDR). We assessed the performances of the test on a collection of strains (n = 54) and a set of clinical samples (n = 242) from routine practice, comparatively to TB diagnosis and genotypic drug susceptibility testing (gDST) as references. Regarding the 242 clinical samples, the sensitivity and specificity of MTB detection by ELITe were 90.9% and 97.5%, respectively. For the detection of resistance-conferring mutations on positive clinical samples, we observed perfect agreement with gDST for katG and pro-inhA (κ = 1.0) and two discordant results for rpoB (κ = 0.82). Considering the 54 cultured strains, very good agreement with gDST was observed for the detection of the 25 distinct mutations in rpoB, katG, and pro-inhA, (κ = 0.95, 0.88, and 0.95, respectively). In conclusion, the automated MDR/MTB ELITe MGB® assay shows great promise and appears to be a valuable tool for rapid detection of pre-MDR- and MDR-TB directly from clinical specimens.

scholarly journals Cost of illness of non-multidrug-resistant tuberculosis in Germany: an update

2020 ◽  
Vol 6 (4) ◽  
pp. 00329-2020
Author(s):  
Roland Diel ◽  
Albert Nienhaus
Keyword(s):  
Central Committee ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Current Therapy ◽  
Productivity Losses ◽  
Public Health Screening ◽  
Mdr Tb ◽  
The Mean ◽  
Mean Cost

BackgroundA total of 5429 new cases of tuberculosis (TB) were reported in Germany in 2018; out of the 3780 TB cases for whom drug susceptibility testing was available, the proportion of multidrug-resistant TB (MDR-TB) cases was only 3.1% (118 cases).MethodsOn the basis of the current therapy guidelines of the German Central Committee against Tuberculosis, this study estimates the mean direct outpatient and combined in- and outpatient costs per non-MDR-TB patient from the perspective of the German statutory health insurance (SHI) system, together with costs arising from productivity losses and costs due to public health screening for TB in close contacts.ResultsFrom the insurance perspective, the mean outpatient costs (rounded) per case were €1628 for adults and €1179 for children for standard therapy; the mean cost of inpatient treatment amounted to €8626. The mean combined inpatient/outpatient cost was €8756 for adults and €8512 for children. As 95% of all TB patients were adults, the weighted treatment cost per patient in Germany in 2018 was €8746. These are in addition to the mean cost arising from productivity losses (€1839) and, weighted by pulmonary infectivity, cost of contact investigations (€368), coming to a total of €10 953.ConclusionGiven the clear increase in the number of non-MDR-TB cases since 2015, TB is still a disease of significant economic impact in Germany.

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.

A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay

2020 ◽  
Vol 51 (6) ◽  
pp. 606-613
Author(s):  
Ye-Cheng Zhou ◽  
Shu-Mei He ◽  
Zi-Lu Wen ◽  
Jun-Wei Zhao ◽  
Yan-Zheng Song ◽  
...  
Keyword(s):  
Clinical Care ◽  
Pcr Amplification ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Hybridization Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.

Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Poor Treatment ◽  
Mdr Tb ◽  
Observational Cohort

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

scholarly journals Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting

2010 ◽  
Vol 139 (11) ◽  
pp. 1784-1793 ◽  
Author(s):  
H. LIN ◽  
S. SHIN ◽  
J. A. BLAYA ◽  
Z. ZHANG ◽  
P. CEGIELSKI ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Urban Setting ◽  
South American ◽  
Resistant Disease ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Incident Cases

SUMMARYWe examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005–2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11 711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.

scholarly journals Disparities in Capreomycin Resistance Levels Associated with therrsA1401G Mutation in Clinical Isolates of Mycobacterium tuberculosis

2014 ◽  
Vol 59 (1) ◽  
pp. 444-449 ◽  
Author(s):  
Analise Z. Reeves ◽  
Patricia J. Campbell ◽  
Melisa J. Willby ◽  
James E. Posey
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Strong Predictor ◽  
Critical Concentration ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Second Line ◽  
Content Type

ABSTRACTAs the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. Performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance for second-line drugs lags behind. TherrsA1401G allele is considered a strong predictor of cross-resistance between the three second-line injectable drugs, capreomycin (CAP), kanamycin, and amikacin. However, discordance is often observed between therrsA1401G mutation and CAP resistance, with up to 40% ofrrsA1401G mutants being classified as CAP susceptible. We measured the MICs to CAP in 53 clinical isolates harboring therrsA1401G mutation and found that the CAP MICs ranged from 8 μg/ml to 40 μg/ml. These results were drastically different from engineered A1401G mutants generated in isogenicMycobacterium tuberculosis, which exclusively exhibited high-level CAP MICs of 40 μg/ml. These data support the results of prior studies, which suggest that the critical concentration of CAP (10 μg/ml) used to determine resistance by indirect agar proportion may be too high to detect all CAP-resistant strains and suggest that a larger percentage of resistant isolates could be identified by lowering the critical concentration. These data also suggest that differences in resistance levels among clinical isolates are possibly due to second site or compensatory mutations located elsewhere in the genome.

scholarly journals Pediatric Tuberculosis in Young Children in India: A Prospective Study

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sanjay K. Jain ◽  
Alvaro Ordonez ◽  
Aarti Kinikar ◽  
Nikhil Gupte ◽  
Madhuri Thakar ◽  
...  
Keyword(s):  
Young Children ◽  
Small Sample Size ◽  
Tertiary Hospital ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Small Sample ◽  
Vulnerable Population ◽  
Poor Outcomes ◽  
Pediatric Tuberculosis ◽  
A Prospective Study

Background. India has one of the highest tuberculosis (TB) burdens globally. However, few studies have focused on TB in young children, a vulnerable population, where lack of early diagnosis results in poor outcomes.Methods. Young children (≤5 years) with suspected TB were prospectively enrolled at a tertiary hospital in Pune, India. Detailed clinical evaluation, HIV testing, mycobacterial cultures, and drug susceptibility testing were performed.Results. 223 children with suspected TB were enrolled. The median age was 31 months, 46% were female, 86% had received BCG, 57% were malnourished, and 10% were HIV positive. 12% had TB disease (definite or probable), 35% did not have TB, while TB could not be ruled out in 53%. Extrapulmonary disease was noted in 46%, which was predominantly meningeal. Tuberculin skin test (TST) was positive in 20% of children with TB. Four of 7 (57%) children with culture-confirmed TB harbored drug-resistant (DR) strains of whom 2 (50%) were multi-DR (MDR). In adjusted analyses, HIV infection, positive TST, and exposure to household smoke were found to be significantly associated with children with TB (P≤0.04). Mortality (at 1 year) was 3 of 26 (12%) and 1 of 79 (1%), respectively, in children with TB and those without TB (P< 0.05).Conclusions. Diagnosis of TB is challenging in young children, with high rates of extra-pulmonary and meningeal disease. While the data on DR-TB are limited by the small sample size, they are however concerning, and additional studies are needed to more accurately define the prevalence of DR strains in this vulnerable population.

scholarly journals Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

2014 ◽  
Vol 53 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Limei Zhu ◽  
Qiao Liu ◽  
Leonardo Martinez ◽  
Jinyan Shi ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Value ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Standard Drug ◽  
Related Data ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

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