Modelling the Transitional Dynamics of Mycobacterium Tuberculosis Strain

The World Health Organization’s targets of eliminating Tuberculosis (TB) by 2050 is challenged by the emergence and spread of drug resistance TB. However, the traditional mechanism of resistance is that of acquired resistance, whereby the mycobacterium Tuberculosis (MTB) strain develops mutations under selective pressure of insufficient drug therapy. These mutations have the tendency of changing the drug target protein, restricting the bacteria to the anti-TB agent. We propose a discrete state markov chain model with three disease states: Drug Susceptible (DS), Multi Drug Resistant (MDR) and Extra Drug Resistant (XDR) to further study the transitional dynamics of the MTB strain. The study made use of a retrospective data on resistant pattern to first line and second line anti TB drugs. The structural properties of the model established life expectancies of DS and MDR strains as well as the probability of first resistance of the DS strain. Key estimates were assessed by the bootstrapping procedure which converged in estimates to the actual data. If the experiment were repeated infinitely many times, in 95 out of 100, the interval 2.782 x 10-7 to 0.018 will contain the true probability of first mutation of the DS strain. A key contribution of this study is the revealing therapeutic cycle of the treatment regime of the TB disease based on the TB progression data which saw the period after the 20th cycle of the treatment being prominent in some key strain dynamics. These findings may also help explain further the pharmacodynamic properties of the "first line" anti-Tuberculosis drugs for enhance TB treatment. Journal of Medical and Biomedical Sciences (2016) 5(2), 13-23

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Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

Journal of Bacteriology & Parasitology ◽

10.4172/2155-9597.1000e128 ◽

2017 ◽

Vol 09 (01) ◽

Author(s):

Suhail Ahmad

Keyword(s):

Mycobacterium Tuberculosis ◽

Susceptibility Testing ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Drug Resistant ◽

First Line ◽

Proper Management ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa

BMC Infectious Diseases ◽

10.1186/s12879-016-1906-3 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 6

Author(s):

Navisha Dookie ◽

A. Willem Sturm ◽

Prashini Moodley

Keyword(s):

South Africa ◽

Mycobacterium Tuberculosis ◽

Antimicrobial Resistance ◽

Drug Resistant ◽

First Line ◽

Extensively Drug Resistant ◽

Kwazulu Natal ◽

Resistant Strains ◽

Drug Resistant Strains

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GeneXpert MTB/RIF Assay for Rapid Identification of Mycobacterium Tuberculosis and Rifampicin Resistance Directly from Sputum Sample

Journal of Enam Medical College ◽

10.3329/jemc.v7i2.32653 ◽

2017 ◽

Vol 7 (2) ◽

pp. 86-89 ◽

Cited By ~ 1

Author(s):

Nourjahan Laskar ◽

Md Akram Hossain ◽

Jannatul Fardows ◽

Mominur Rahman

Keyword(s):

Mycobacterium Tuberculosis ◽

Sputum Sample ◽

Rapid Identification ◽

Rapid Diagnosis ◽

World Health ◽

Multi Drug Resistance ◽

Drug Resistant ◽

Resistant Tuberculosis ◽

The World ◽

Health Organization

Background: The World Health Organization has endorsed the use of molecular methods for the detection of tuberculosis (TB) and drug resistant TB as a rapid method. In Bangladesh, the Xpert MTB/RIF assay has been implemented into reference laboratories for diagnosis of TB and also MDR TB.Objective: Drug resistant tuberculosis has long been a common problem prevailing in our country. The present study focused on the rapid identification of Mycobacterium tuberculosis as well as drug resistance.Materials and Methods: Sputum samples from a total of 107 cases, assumed as multi-drug resistance tuberculosis, were studied through GeneXpert assay.Results: Out of 107 cases, 91 (85.05%) were detected having M. tuberculosis ? 64 (59.81%) were rifampicin sensitive and 27 (25.23%) were rifampicin resistant. The sensitivity and specificity of the GeneXpert are 87.64% and 75% respectively.Conclusion: GeneXpert assay can be considered for the rapid diagnosis of drug resistant tuberculosis.J Enam Med Col 2017; 7(2): 86-89

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Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus

Journal of Clinical Microbiology ◽

10.1128/jcm.02116-16 ◽

2016 ◽

Vol 55 (2) ◽

pp. 457-469 ◽

Cited By ~ 22

Author(s):

Kurt R. Wollenberg ◽

Christopher A. Desjardins ◽

Aksana Zalutskaya ◽

Vervara Slodovnikova ◽

Andrew J. Oler ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

De Novo ◽

Acquired Resistance ◽

Multiple Infections ◽

Drug Resistant ◽

Genetic Composition ◽

Hiv Patients ◽

Treatment Protocols ◽

Content Type ◽

Phenotypic Resistance

ABSTRACTThe emergence and spread of drug-resistantMycobacterium tuberculosis(DR-TB) are critical global health issues. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138M. tuberculosisisolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB. Using a phylogenomic approach, we estimated that the majority of MDR-TB was due to the recent transmission of already-resistantM. tuberculosisstrains rather than repeatedde novoevolution of resistance within patients, while XDR-TB was acquired through both routes. Longitudinal sampling ofM. tuberculosisfrom 34 patients with treatment failure showed that most strains persisted genetically unchanged during treatment or acquired resistance to fluoroquinolones. HIV+ patients were significantly more likely to have multiple infections over time than HIV− patients, highlighting a specific need for careful infection control in these patients. These data provide a better understanding of the genomic composition, transmission, and evolution of MDR- and XDR-TB in Belarus and will enable improved diagnostics, treatment protocols, and prognostic decision-making.

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Peer Review #1 of "Rapid screening mutations of first-line-drug-resistant genes in Mycobacterium tuberculosis strains by allele-specific real-time quantitative PCR (v0.2)"

10.7287/peerj.6696v0.2/reviews/1 ◽

2019 ◽

Keyword(s):

Mycobacterium Tuberculosis ◽

Peer Review ◽

Quantitative Pcr ◽

Rapid Screening ◽

Drug Resistant ◽

First Line ◽

Real Time Quantitative Pcr ◽

Resistant Genes ◽

Allele Specific ◽

Line Drug

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Simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol in fixed-dose combination antituberculosis pharmaceutical formulations: a review

Analytical Methods ◽

10.1039/c7ay02686b ◽

2018 ◽

Vol 10 (10) ◽

pp. 1103-1116 ◽

Cited By ~ 3

Author(s):

M. A. L. Oliveira ◽

P. R. Chellini ◽

T. L. Amorim

Keyword(s):

Infectious Disease ◽

Mycobacterium Tuberculosis ◽

Pharmaceutical Formulations ◽

World Health ◽

Fixed Dose ◽

First Line ◽

The World ◽

Dose Combination ◽

Health Organization

According to the World Health Organization, rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are the first-line drugs used to treat tuberculosis – an infectious disease caused by Mycobacterium tuberculosis.

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First-line tuberculosis therapy and drug-resistant Mycobacterium tuberculosis in prisons

The Lancet ◽

10.1016/s0140-6736(98)08341-x ◽

1999 ◽

Vol 353 (9157) ◽

pp. 969-973 ◽

Cited By ~ 72

Author(s):

R Coninx ◽

C Mathieu ◽

M Debacker ◽

F Mirzoev ◽

A Ismaelov ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Resistant ◽

First Line ◽

Tuberculosis Therapy

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Tuberculosis drug resistance in Canada, 1998 to 2000

Canadian Journal of Infectious Diseases ◽

10.1155/2001/148487 ◽

2001 ◽

Vol 12 (3) ◽

pp. 141-143

Author(s):

Melissa D Phypers ◽

Linda Panaro ◽

Penny Nault

Keyword(s):

World Health ◽

Drug Resistant ◽

First Line ◽

International Union ◽

The World ◽

Resistant Strains ◽

Health Organization ◽

Global Threat ◽

Drug Resistant Strains ◽

And Control

The emergence of drug-resistant strains of tuberculosis (TB) is a global threat to TB prevention and control efforts. A recent study conducted by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease found strains of TB resistant to first-line anti-TB drugs in all countries surveyed (1). The WHO estimates that 50 million people are infected with strains of drug-resistant TB (2).

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