Evidence map›Paper›PMID 35585607›Full record

ArticleGenome medicine2022

Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing.

Doctor B Sibandze, Alexander Kay, Viola Dreyer, Welile Sikhondze, Qiniso Dlamini, Andrew DiNardo, Godwin Mtetwa, Bhekumusa Lukhele, Debrah Vambe, Christoph Lange and 11 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
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  3. Use of reverse dot blot hybridization DNA-array and targeted next-generation sequencing for the detection of drug resistance in patients with tuberculosis: a prospective diagnostic accuracy study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 5 countries.

Doctor B Sibandze *National Tuberculosis Reference Laboratory, Eswatini National Health Services Laboratory, Ministry of Health, Mbabane, Eswatini.
Alexander Kay *Baylor College of Medicine Children's Foundation-Eswatini, Mbabane, Eswatini. Alexander.kay@bcm.edu.ORCID http://orcid.org/0000-0001-5283-4697
Viola Dreyer *Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
Welile Sikhondze *Department of Global Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Qiniso DlaminiBaylor College of Medicine Children's Foundation-Eswatini, Mbabane, Eswatini.
Andrew DiNardoGlobal Tuberculosis Program, Baylor College of Medicine, Houston, TX, USA.
Godwin MtetwaBaylor College of Medicine Children's Foundation-Eswatini, Mbabane, Eswatini.
Bhekumusa LukheleBaylor College of Medicine Children's Foundation-Eswatini, Mbabane, Eswatini.
Debrah VambeEswatini National Tuberculosis Program, Ministry of Health, Mbabane, Eswatini.
Christoph LangeGlobal Tuberculosis Program, Baylor College of Medicine, Houston, TX, USA.
Muyalo Glenn DlaminiNational Tuberculosis Reference Laboratory, Eswatini National Health Services Laboratory, Ministry of Health, Mbabane, Eswatini.
Tara NessGlobal Tuberculosis Program, Baylor College of Medicine, Houston, TX, USA.
Rojelio MejiaThe National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
Barbara KalsdorfGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.
Jan HeyckendorfGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.
Martin KuhnsNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
Florian P MaurerGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.
Sindisiwe DlaminiNational Tuberculosis Reference Laboratory, Eswatini National Health Services Laboratory, Ministry of Health, Mbabane, Eswatini.
Gugu MaphalalaNational Tuberculosis Reference Laboratory, Eswatini National Health Services Laboratory, Ministry of Health, Mbabane, Eswatini.
Stefan Niemann *Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
Anna Mandalakas *Global Tuberculosis Program, Baylor College of Medicine, Houston, TX, USA. Anna.mandalakas@bcm.edu.
Baylor College of Medicine · USMinistry of Health · SZGerman Center for Infection Research · DEAmsterdam University Medical Centers · NLResearch Center Borstel - Leibniz Lung Center · DEUniversität Hamburg · DEUniversity Hospital Schleswig-Holstein · DE

Funding

Quantifiable stool-based TB PCR to Improve Diagnostics and Treatment MonitoringR01AI137527 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI MANDALAKAS, ANNA M · 2019 to 2022
$2.7M
Persistent DNA Hyper-Methylation of the IFN-γ Signaling Pathway During TuberculosisK23AI141681 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI DINARDO, ANDREW R · 2019 to 2023
$947k
Developing Clinical Prediction Tools to Define Strategies for Differentiated Service Delivery in Children and Adolescents Living with HIV in sub-Saharan Africa.K01TW011482 · FIC · BAYLOR COLLEGE OF MEDICINE · PI KAY, ALEXANDER WILLIAM · 2020 to 2024
$749k
FIC NIH HHS K01 TW011482National Institute of Allergy and Infectious Diseases R01AI137527NIAID NIH HHS K23 AI141681NIAID NIH HHS R01 AI137527
6 · The paper itself

Abstract

backgroundStool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.

methodsWe evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a prospective cohort of patients treated for tuberculosis in Eswatini (n = 66; 56 with and 10 participants without M. tuberculosis complex DNA detected in stool by real-time quantitative PCR), and an independent German validation cohort of participants with culture-confirmed tuberculosis (n = 21).

resultsThe tNGS assay detected M. tuberculosis complex DNA in 38 of 56 (68%) samples; for 28 of 38 (74%) samples, a full M. tuberculosis complex drug resistance prediction report was obtained. There was a high degree of concordance with sputum phenotypic drug susceptibility results (κ = 0.82). The ability to predict resistance was concentration-dependent and successful in 7/10 (70%), 18/25 (72%), and 3/21 (14%) of samples with stool PCR concentration thresholds of > 100 femtogram per microliter (fg/μl), 1 to 100 fg/μl, and < 1 fg/μl, respectively (p = 0.0004). The German cohort confirmed these results and demonstrated a similarly high concordance between stool tNGS and sputum phenotypic drug susceptibility results (κ = 0.84).

conclusionstNGS can identify drug resistance from stool provided by tuberculosis patients. This affords the opportunity to obtain critical diagnostic information for tuberculosis patients who struggle to provide respiratory specimens.

Indexed as

Mycobacterium tuberculosisTuberculosisAntitubercular AgentsChildDNAHumansPathology, MolecularProspective StudiesReal-Time Polymerase Chain ReactionSensitivity and SpecificityAntitubercular AgentsDNADrug resistanceFecesTuberculosis

Identifiers

PMID35585607
PMCPMC9118838
OpenAlexW4280561902

What OpenQuestion holds

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Registered trials

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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.