Evidence map›Paper›PMID 27576542›Full record

ArticleBMC infectious diseases2016

Shedding light on the performance of a pyrosequencing assay for drug-resistant tuberculosis diagnosis.

Sophia B Georghiou, Marva Seifert, Shou-Yean Lin, Donald Catanzaro, Richard S Garfein, Roberta L Jackson, Valeriu Crudu, Camilla Rodrigues, Thomas C Victor, Antonino Catanzaro and 1 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02170441 (Global Consortium for Drug-resistant Tuberculosis Diagnostics), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02170441 completednot on this map

Global Consortium for Drug-resistant Tuberculosis Diagnostics

TypeobservationalSponsorUniversity of California, San DiegoRan2012 to 2014Enrolled1,128ConditionsTuberculosis, Tuberculosis, Multidrug-Resistant
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 4 countries.

Sophia B GeorghiouDepartment of Medicine, University of California San Diego, La Jolla, CA, USA. sgeorghi@ucsd.edu.
Marva SeifertDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Shou-Yean LinCalifornia Department of Public Health, Richmond, CA, USA.
Donald CatanzaroUniversity of Arkansas, Fayetteville, AR, USA.
Richard S GarfeinDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Roberta L JacksonDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Valeriu CruduMicrobiology and Morphology Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova.
Camilla RodriguesDepartment of Microbiology, P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India.
Thomas C VictorDivision of Molecular Biology and Human Genetics, Stellenbosch University, Stellenbosch, South Africa.
Antonino CatanzaroDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Timothy C RodwellDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
University of California, San Diego · USCalifornia Department of Public Health · USP. D. Hinduja Hospital and Medical Research Centre · INPhthisiopneumology Institute "Chiril Draganiuc" · MDStellenbosch University · ZAUniversity of Arkansas at Fayetteville · US

Funding

Rapid Tests for Drug Resistance to Detect Extensively Drug-Resistant TuberculosisU01AI082229 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CATANZARO, ANTONINO · 2009 to 2013
$10.9M
An Integrated Tabletop Platform for Rapid Detection of XDR-TB in Clinical SamplesR01AI111435 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RODWELL, TIMOTHY CHARLES · 2014 to 2018
$5.4M
Training in the Next Generation in Respiratory ScienceT32HL134632 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALHOTRA, ATUL, POWELL, FRANK L. · 2017 to 2021
$2.1M
Training in Respiratory Biology: Innovate, Integrate, and TranslateT32HL098062 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POWELL, FRANK L. · 2010 to 2014
$2.1M
NHLBI NIH HHS T32 HL098062NHLBI NIH HHS T32 HL134632NIAID NIH HHS R01 AI111435NIAID NIH HHS U01 AI082229
6 · The paper itself

Abstract

backgroundRapid molecular diagnostics, with their ability to quickly identify genetic mutations associated with drug resistance in Mycobacterium tuberculosis clinical specimens, have great potential as tools to control multi- and extensively drug-resistant tuberculosis (M/XDR-TB). The Qiagen PyroMark Q96 ID system is a commercially available pyrosequencing (PSQ) platform that has been validated for rapid M/XDR-TB diagnosis. However, the details of the assay's diagnostic and technical performance have yet to be thoroughly investigated in diverse clinical environments.

methodsThis study evaluates the diagnostic performance of the PSQ assay for 1128 clinical specimens from patients from three areas of high TB burden. We report on the diagnostic performance of the PSQ assay between the three sites and identify variables associated with poor PSQ technical performance.

resultsIn India, the sensitivity of the PSQ assay ranged from 89 to 98 % for the detection of phenotypic resistance to isoniazid, rifampicin, fluoroquinolones, and the injectables. In Moldova, assay sensitivity ranged from 7 to 94 %, and in South Africa, assay sensitivity ranged from 71 to 92 %. Specificity was high (94-100 %) across all sites. The addition of eis promoter sequencing information greatly improved the sensitivity of kanamycin resistance detection in Moldova (7 % to 79 %). Nearly all (89.4 %) sequencing reactions conducted on smear-positive, culture-positive specimens and most (70.8 %) reactions conducted on smear-negative, culture-positive specimens yielded valid PSQ reads. An investigation into the variables influencing sequencing failures indicated smear negativity, culture negativity, site (Moldova), and sequencing of the rpoB, gyrA, and rrs genes were highly associated with poor PSQ technical performance (adj. OR > 2.0).

conclusionsThis study has important implications for the global implementation of PSQ as a molecular TB diagnostic, as it demonstrates how regional factors may impact PSQ diagnostic performance, while underscoring potential gene targets for optimization to improve overall PSQ assay technical performance.

trial registrationClinicalTrials.gov ( #NCT02170441 ). Registered 12 June 2014.

Indexed as

Antitubercular AgentsExtensively Drug-Resistant TuberculosisFluoroquinolonesGenes, BacterialHumansIsoniazidKanamycinKanamycin ResistanceMicrobial Sensitivity TestsMolecular Diagnostic TechniquesMolecular TypingMutationMycobacterium tuberculosisPromoter Regions, GeneticRifampinSensitivity and SpecificityAntitubercular AgentsFluoroquinolonesIsoniazidKanamycinRifampinDrug-resistant tuberculosisMolecular diagnosticsPerformance evaluationPyrosequencing

Identifiers

PMID27576542
PMCPMC5006534
OpenAlexW2517119434

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.