Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery

Molloy, Antonia; Harrison, James; McGrath, John S.; Owen, Zachary; Smith, Clive A.; Liu, Xin; Li, Xin; Cox, Jonathan

doi:10.3390/microorganisms9112330

Cited by 10 publications

(4 citation statements)

References 174 publications

(193 reference statements)

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“…Positron emission tomography (PET) imaging has brought to light the heterogeneity of TB lesions in live animals and humans ( Lenaerts et al., 2015 ). Microfluidics ( Molloy et al., 2021 ) and time-lapse microscopy ( Herricks et al., 2020 ) are revealing the complexity of Mtb populations in vitro , and reporter gene technology ( Huang et al., 2019 ) is providing similar insights in vivo .…”

Section: Discussionmentioning

confidence: 99%

The evolving biology of Mycobacterium tuberculosis drug resistance

Jones

Adams

Eldesouky

et al. 2022

Front. Cell. Infect. Microbiol.

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Tuberculosis, caused by Mycobacterium tuberculosis (Mtb) is an ancient disease that has remained a leading cause of infectious death. Mtb has evolved drug resistance to every antibiotic regimen ever introduced, greatly complicating treatment, lowering rates of cure and menacing TB control in parts of the world. As technology has advanced, our understanding of antimicrobial resistance has improved, and our models of the phenomenon have evolved. In this review, we focus on recent research progress that supports an updated model for the evolution of drug resistance in Mtb. We highlight the contribution of drug tolerance on the path to resistance, and the influence of heterogeneity on tolerance. Resistance is likely to remain an issue for as long as drugs are needed to treat TB. However, with technology driving new insights and careful management of newly developed resources, antimicrobial resistance need not continue to threaten global progress against TB, as it has done for decades.

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Section: Discussionmentioning

confidence: 99%

The evolving biology of Mycobacterium tuberculosis drug resistance

Jones

Adams

Eldesouky

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Utility was initially limited in low-income countries by cost and requirement for robust facilities and technical expertise [38]. However, with ongoing technological advancements in the microfluidic approaches to TB diagnosis, WGS is likely to be available at point of care on a global basis [39]. For some countries, it remains an important tool not only in case diagnosis, but in formulating public health policy by assisting in tracing TB contact cases in outbreaks [40].…”

Section: Whole Genome Sequencing (Wgs)mentioning

confidence: 99%

New developments in tuberculosis diagnosis and treatment

Gill

Dolan

Piggott

et al. 2022

Breathe

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Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. It is estimated that 25% of the world's population are infected with Mycobacterium tuberculosis, with a 5–10% lifetime risk of progression into TB disease. Early recognition of TB disease and prompt detection of drug resistance are essential to halting its global burden. Culture, direct microscopy, biomolecular tests and whole genome sequencing are approved methods of diagnosis; however, their widespread use is often curtailed owing to costs, local resources, time constraints and operator efficiency. Methods of optimising these diagnostics, in addition to developing novel techniques, are under review. The selection of an appropriate drug regimen is dependent on the susceptibility pattern of the isolate detected. At present, there are 16 new drugs under evaluation for TB treatment in phase I or II clinical trials, with an additional 22 drugs in preclinical stages. Alongside the development of these new drugs, most of which are oral medications, new shorter regimes are under evaluation. The aim of these shorter regimens is to encourage patient adherence, and prevent relapse or the evolution of further drug resistance. Screening for TB infection, especially in vulnerable populations, provides an opportunity for intervention prior to progression towards infectious TB disease. New regimens are currently under evaluation to assess the efficacy of shorter durations of treatment in this population. In addition, there is extensive research into the use of post-exposure vaccinations in this cohort. Worldwide collaboration and sharing of expertise are essential to our ultimate aim of global eradication of TB disease.Educational aimsDifferentiate between TB infection and TB disease.Understand the different methods of diagnosing TB disease and resistance.Recognise the different drugs and regimens currently in use for TB disease.Be able to discuss risk of TB disease in TB infection, and assist patients in making an informed decision on treatment for TB infection.

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“…10 Fully automated PoC solutions with detection of MTBC and Rif and Inh resistances are still under development. [11][12][13] A lab-on-a-film platform that integrates sample preparation and detection of MTBC and Rif and Inh resistance markers was demonstrated by Kukhtin et al 14 Its long time to result of 8 h and a complex instrumental setup, however, challenge its use as a PoC test.…”

Section: Introductionmentioning

confidence: 99%