For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
6
views
107
references
 Top references
cited by
9
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      1,433
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found

      The development, evaluation and performance of molecular diagnostics for detection of Mycobacterium tuberculosis

      Author(s): ,
      Publication date Created:
      Publication date (Electronic):
      Journal: Expert Review of Molecular Diagnostics
      Publisher: Informa UK Limited

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impact of TB diagnostics.

          Related collections

          Most cited references107

          • Record: found
          • Abstract: found
          • Article: not found

          Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis.

          Karen Steingart, Nandini Dendukuri, Madhukar Pai … (2014)
          Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is endorsed for the detection of pulmonary tuberculosis (TB). We performed a systematic review and meta-analysis to assess the accuracy of Xpert for the detection of extrapulmonary TB. We searched multiple databases to October 15, 2013. We determined the accuracy of Xpert compared with culture and a composite reference standard (CRS). We grouped data by sample type and performed meta-analyses using a bivariate random-effects model. We assessed sources of heterogeneity using meta-regression for predefined covariates. We identified 18 studies involving 4461 samples. Sample processing varied greatly among the studies. Xpert sensitivity differed substantially between sample types. In lymph node tissues or aspirates, Xpert pooled sensitivity was 83.1% (95% CI 71.4-90.7%) versus culture and 81.2% (95% CI 72.4-87.7%) versus CRS. In cerebrospinal fluid, Xpert pooled sensitivity was 80.5% (95% CI 59.0-92.2%) against culture and 62.8% (95% CI 47.7-75.8%) against CRS. In pleural fluid, pooled sensitivity was 46.4% (95% CI 26.3-67.8%) against culture and 21.4% (95% CI 8.8-33.9%) against CRS. Xpert pooled specificity was consistently >98.7% against CRS across different sample types. Based on this systematic review, the World Health Organization now recommends Xpert over conventional tests for diagnosis of TB in lymph nodes and other tissues, and as the preferred initial test for diagnosis of TB meningitis. ©ERS 2014.
          Article 0 comments Cited 177 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis.

            Anne K Detjen, Andrew R DiNardo, Jacinta Leyden … (2015)
            Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. We aimed to establish summary estimates for sensitivity and specificity of of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children.
            Article 0 comments Cited 126 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study

              Stephen D Lawn, Andrew D Kerkhoff, Monica Vogt … (2012)
              Summary Background The diagnostic accuracy of sputum smear microscopy and routine chest radiology for HIV-associated tuberculosis is poor, and culture-based diagnosis is slow, expensive, and is unavailable in most resource-limited settings. We assessed the diagnostic accuracy of a urine antigen test Determine TB-LAM Ag (Determine TB-LAM; Alere, Waltham, MA, USA) for screening for HIV-associated pulmonary tuberculosis before antiretroviral therapy (ART). Methods In this descriptive study, consecutive adults referred to a community-based ART clinic in Gugulethu township, South Africa, were all screened for tuberculosis by obtaining sputum samples for fluorescence microscopy, automated liquid culture (gold-standard test), and Xpert MTB/RIF assays (Cepheid, Sunnyvale, CA, USA) and urine samples for the Clearview TB-ELISA (TB-ELISA; Alere, Waltham, MA, USA) and Determine TB-LAM test. Patients with Mycobacterium tuberculosis cultured from one or more sputum samples were defined as cases of tuberculosis. The diagnostic accuracy of Determine TB-LAM used alone or combined with sputum smear microscopy was compared with that of sputum culture and the Xpert MTB/RIF assay for all patients and subgroups of patients stratified by CD4 cell count. Findings Patients were recruited between March 12, 2010, and April 20, 2011. Of 602 patients enrolled, 542 were able to provide one or more sputum samples, and 94 had culture-positive tuberculosis (prevalence 17·4%, 95% CI 14·2–20·8). Complete results from all tests were available for 516 patients (median CD4 count, 169·5 cells per μL; IQR 100–233), including 85 culture-positive tuberculosis, 24 of whom (28·2%, 95% CI 19·0–39·0) had sputum smear-positive disease. Determine TB-LAM test strips provided results within 30 min. Agreement was very high between two independent readers of the test strips (κ=0·97) and between the test strips and TB-ELISA (κ=0·84). Determine TB-LAM had highest sensitivity at low CD4 cell counts: 66·7% (95% CI 41·0–86·7) at <50 cells per μL, 51·7% (32·5–70·6) at <100 cells per μL, and 39·0% (26·5–52·6) at <200 cells per μL; specificity was greater than 98% for all strata. When combined with smear microscopy (either test positive), sensitivity was 72·2% (95% CI 46·5–90·3) at CD4 counts less than 50 cells per μL, 65·5% (45·7–82·1) at less than 100 cells per μL, and 52·5% (39·1–65·7) at less than 200 cells per μL, which did not differ statistically from the sensitivities obtained by testing a single sputum sample with the Xpert MTB/RIF assay. Interpretation Determine TB-LAM is a simple, low-cost, alternative to existing diagnostic assays for tuberculosis screening in HIV-infected patients with very low CD4 cell counts and provides important incremental yield when combined with sputum smear microscopy. Funding Wellcome Trust.
              Article 0 comments Cited 122 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Expert Review of Molecular Diagnostics
                Abbreviated Title: Expert Review of Molecular Diagnostics
                Publisher: Informa UK Limited
                ISSN (Print): 1473-7159
                ISSN (Electronic): 1744-8352
                Publication date Created: January 11 2016
                Publication date Created: March 03 2016
                Publication date (Electronic): February 17 2016
                Publication date (Print): March 03 2016
                Volume: 16
                Issue: 3
                Pages: 307-322
                Article
                DOI: 10.1586/14737159.2016.1139457
                PubMed ID: 26735769
                SO-VID: bc368741-890a-4dee-b70c-f65d697171a8
                Copyright © © 2016
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content1,433

                See all similar

                Cited by8

                See all cited by

                Most referenced authors1,244

                See all reference authors