The Potential for Testing Stool to Reduce Tuberculosis Missed Diagnoses and Misdiagnoses

Datta, Sumona; Gonzales-Huerta, Luis; Evans, Carlton A.

doi:10.4269/ajtmh.18-0507

Cited by 2 publications

(3 citation statements)

References 24 publications

(26 reference statements)

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“…Stool samples can be used as a substitute for respiratory specimens in the diagnosis of PTB. 20 When sputum is swallowed and MTB passes through the digestive tract, microscopy, culture and PCR testing, including the Xpert assay, can detect MTB in stool specimens. 21 22 Recent systematic reviews on PTB diagnosis in paediatric patients using the Xpert and other PCR-based assays on stool samples have shown high specificity with moderate sensitivity and suggest using stool samples as a rule-in test for PTB diagnosis in children.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, a non-invasive approach for diagnosing PTB without sputum would benefit these critical patient groups. Stool samples can be used as a substitute for respiratory specimens in the diagnosis of PTB 20. When sputum is swallowed and MTB passes through the digestive tract, microscopy, culture and PCR testing, including the Xpert assay, can detect MTB in stool specimens 21 22.…”

Section: Introductionmentioning

confidence: 99%

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Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review

Sultana¹,

Afrin²,

Hasan³

et al. 2023

BMJ Open

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ObjectiveTo assess the diagnostic accuracy of stool specimens to diagnose pulmonary tuberculosis (PTB) in adults.DesignSystematic review.Data sourcesMEDLINE (Ovid), Embase (Ovid), Web of Science and the Cochrane database were searched from inception to 9 March 2023–10 March 2023 using a comprehensive search strategy; reference lists of selected articles and relevant review articles were manually searched.Eligibility criteria for selecting studiesStudies in English reporting diagnostic performance of stool specimens against respiratory specimens using mycobacterial culture or smear microscopy or Xpert assay to diagnose PTB in adults were eligible for this systematic review.Data extraction and synthesisTwo reviewers independently screened the retrieved citations and extracted data. The risk of bias and applicability of results were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Narrative data synthesis was performed.ResultsA total of 1658 citations were screened, and 28 full-text articles were assessed. Nine studies met the inclusion criteria. The reported sensitivity and specificity of stool culture varied between 21.4% and 63.9%, and 61.5% and 100%, respectively. In stool smear microscopy, sensitivities and specificities ranged from 12.1% to 53.9%, and from 79.5% to 100%, respectively. The reported sensitivities of PCR assays, including Xpert assays, ranged from 69.7% to 100%, with specificities ranging from 69.8% to 100%. Most of the studies had a low risk of bias and a low applicability concern in all domains.ConclusionThis systematic review could not conclude on the diagnostic accuracy of stool specimens for PTB diagnosis in adults. Further studies are required to evaluate the accuracy of stool specimens in adults to enable meta-analyses in updates of this review as well as other systematic reviews.PROSPERO registration numberCRD42021245203.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review

Sultana¹,

Afrin²,

Hasan³

et al. 2023

BMJ Open

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“…However, GeneXpert is relatively expensive (≥$10 per test after hardware) and requires operator training, instrument upkeep, and calibration [ 2 ]. Furthermore, not all patients have TB disease that leads to sputum production, including children and HIV positive individuals, making timely diagnosis of these populations particularly challenging [ 3 – 5 ]. Reducing reliance on sputum, utilizing alternative sample sources, considering alternative TB and TB disease biomarkers, assay simplification, and decreasing cost are all important parameters that will lead to novel diagnostics that inform an affordable POC test.…”

Section: Introductionmentioning

confidence: 99%

Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis

et al. 2019

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BackgroundTimely diagnosis of tuberculosis disease is critical for positive patient outcomes, yet potentially millions go undiagnosed or unreported each year. Sputum is widely used as the testing input, but limited by its complexity, heterogeneity, and sourcing problems. Finding methods to interrogate noninvasive, non-sputum clinical specimens is indispensable to improving access to tuberculosis diagnosis and care. In this work, economical plasmonic gratings were used to analyze tuberculosis biomarker lipoarabinomannan (LAM) from clinical urine samples by single molecule fluorescence assay (FLISA) and compared with gold standard sputum GeneXpert MTB/ RIF, culture, and reference ELISA testing results.Methods and FindingsIn this study, twenty sputum and urine sample sets were selected retrospectively from a repository of HIV-negative patient samples collected before initiation of anti-tuberculosis therapy. GeneXpert MTB/RIF and culture testing of patient sputum confirmed the presence or absence of pulmonary tuberculosis while all patient urines were reference ELISA LAM-negative. Plasmonic gratings produced by low-cost soft lithography were bound with anti-LAM capture antibody, incubated with patient urine samples, and biotinylated detection antibody. Fluorescently labeled streptavidin revealed single molecule emission by epifluorescence microscope. Using a 1 fg/mL baseline for limit of detection, single molecule FLISA demonstrated good qualitative agreement with gold standard tests on 19 of 20 patients, including accurately predicting the gold-standard-negative patients, while one gold-standard-positive patient produced no observable LAM in urine.ConclusionsSingle molecule FLISA by plasmonic grating demonstrated the ability to quantify tuberculosis LAM from complex urine samples of patients from a high endemic setting with negligible interference from the complex media itself. Moreover, agreement with patient diagnoses by gold standard testing suggests that single molecule FLISA could be used as a highly sensitive test to diagnose tuberculosis noninvasively.

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The Potential for Testing Stool to Reduce Tuberculosis Missed Diagnoses and Misdiagnoses

Cited by 2 publications

References 24 publications

Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review

Stool specimen for diagnosis of pulmonary tuberculosis in adults: a systematic review

Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis

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