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Detecting Drug-Resistant Tuberculosis

The Importance of Rapid Testing

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Abstract

Despite numerous intervention strategies, including the direct observed short-course treatment strategy and improved diagnostic methods, the incidence of multidrug-resistant and extensively drug-resistant tuberculosis (TB) continues to rise globally.

Many treatment policies are based on the model that acquisition of drug resistance in already infected individuals drives the drug-resistant TB epidemic, hence the focus on drug-resistance testing of retreatment cases. However, molecular epidemiology and mathematical modeling suggest that the majority of multidrug-resistant TB cases are due to ongoing transmission of multidrug-resistant strains. This is most likely the result of diagnostic delay, thereby emphasizing the need for rapid diagnostics and comprehensive contact tracing, as well as active case finding.

Current diagnosis of TB in low-income, high-burden regions relies on smear microscopy and clinical signs and symptoms. However, this smear-centered approach has many pitfalls, including low sensitivity in HIV patients and children, the inability of smear to reveal drug-resistance patterns, and the need for sampling on consecutive days.

In order to address these limitations, efforts have been made to expand access to Mycobacterium tuberculosis culture and drug susceptibility testing. However, the slow growth rate of the causative agent, M. tuberculosis, contributes to significant diagnostic delay.

Molecular-based diagnostic methods, targeting mutations that are known to confirm drug resistance, are capable of significantly reducing diagnostic delay. Two such methods, the line-probe assay and the real-time PCR-based Xpert® MTB/RIF assay, have been described. The latter test shows particular promise for smear-negative and extrapulmonary specimens. This may prove especially useful in settings where co-infection rates with HIV are high. However, since most research focuses on the performance of both of these assays, further investigations need to be done regarding the impact of the routine implementation of these assays on TB control programs and the cost effectiveness thereof.

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Acknowledgments

No sources of funding were used to prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Division of Medical Microbiology, Department of Pathology, University of Stellenbosch, Tygerberg, South Africa

    Kim G. P. Hoek

  2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Annelies Van Rie

  3. Department of Science and Technology/National Research Foundation (DST/NRF) Centre of Excellence for Biomedical Tuberculosis Research and Medical Research Council (MRC) Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, University of Stellenbosch, Tygerberg, South Africa

    Paul D. van Helden, Robin M. Warren &  Thomas C. Victor

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  1. Kim G. P. Hoek
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Correspondence to Thomas C. Victor.

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Hoek, K.G.P., Van Rie, A., van Helden, P.D. et al. Detecting Drug-Resistant Tuberculosis. Mol Diag Ther 15, 189–194 (2011). https://doi.org/10.1007/BF03256410

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