Evidence map›Paper›PMID 41192929›Full record

Observational studyBMJ global health2025

Targeted next-generation sequencing for drug-resistant tuberculosis diagnosis: implementation considerations for bacterial load, regimen selection and diagnostic algorithm placement.

Sophia B Georghiou, Nestani Tukvadze, Camilla Rodrigues, Shaheed Vally Omar, Andrea Maurizio Cabibbe, Marva Seifert, Swapna Uplekar, Nazir Ismail, Morten Ruhwald, Anita Suresh and 1 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in BMJ global health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04239326 (Multicentre Clinical Trial to Assess the Performance of Culture-free, End-to-end Targeted NGS), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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.

NCT04239326 completednot on this map

Multicentre Clinical Trial to Assess the Performance of Culture-free, End-to-end Targeted NGS (tNGS) Solutions for Diagnosis of Drug Resistant TB (DR-TB)

TypeobservationalSponsorFoundation for Innovative New Diagnostics, SwitzerlandRan2021 to 2023Enrolled800ConditionsTuberculosis, Multidrug-ResistantArmstargeted Next Generation Sequencing (tNGS)
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
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.

Sophia B GeorghiouFIND, Geneva, Switzerland sgeorghiou@gmail.com.ORCID 0000-0003-0099-903X
Nestani TukvadzeNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Camilla RodriguesPD Hinduja National Hospital and Medical Research Centre, Mumbai, India.
Shaheed Vally OmarNational Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.
Andrea Maurizio CabibbeIRCCS Ospedale San Raffaele, Milan, Italy.ORCID 0000-0001-9727-6465
Marva SeifertFIND, Geneva, Switzerland.
Swapna UplekarFIND, Geneva, Switzerland.
Nazir IsmailFaculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0001-7696-3776
Morten RuhwaldFIND, Geneva, Switzerland.
Anita SureshFIND, Geneva, Switzerland.
Rebecca E ColmanFIND, Geneva, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEarly and accurate diagnosis of drug-resistant tuberculosis (DR-TB) is essential for improving treatment outcomes. Phenotypic drug susceptibility testing (pDST) is comprehensive but slow, while rapid molecular assays provide resistance information for a limited number of drugs. Targeted next-generation sequencing (tNGS) offers the potential for broad and rapid resistance detection, but its integration into diagnostic algorithms has been hindered by uncertainty about its placement within existing workflows.

methodsThis study evaluated the extent to which two tNGS solutions-Deeplex Myc-TB (GenoScreen) and TB Drug Resistance Test (Oxford Nanopore Technologies, ONT)-provided interpretable drug resistance results that could inform regimen design, in comparison to other WHO-recommended molecular assays and pDST. Data were collected from three high-burden DR-TB settings under the Seq&Treat study. Sequencing success rates and drug resistance detection were analysed based on: (1) the initial Xpert MTB/RIF result (very low, low, medium, high), (2) resistance results for drugs in WHO-recommended regimens and (3) performance relative to other WHO-endorsed assays. The potential impact of different algorithms on the estimates was also considered. Key factors influencing successful tNGS adoption within diagnostic pathways were identified, leveraging insights from the Seq&Treat diagnostic accuracy study.

resultsSequencing success rates were 88.5% (GenoScreen) and 93.1% (ONT) across 763 samples. While tNGS provided complete resistance data for 73%-86% of drugs in recommended regimens, pDST achieved 92%-93%. Both tNGS solutions matched or exceeded the sensitivity of WHO-recommended molecular assays.

conclusionsThis study highlights the critical role of tNGS as a centralised tool for comprehensive drug resistance testing to inform DR-TB treatment decisions following initial screening assays. By complementing existing molecular tests with tNGS, diagnostic workflows can be optimised to ensure timely and comprehensive resistance detection. These findings support policy updates to integrate tNGS into global TB diagnostic algorithms. TRIAL REGISTRATION NUMBER: NCT04239326.

Indexed as

AlgorithmsHigh-Throughput Nucleotide SequencingMycobacterium tuberculosisTuberculosis, Multidrug-ResistantAntitubercular AgentsHumansMicrobial Sensitivity TestsAntitubercular AgentsDiagnostics and toolsGlobal HealthOther diagnostic or toolRespiratory infectionsTuberculosis

Identifiers

PMID41192929
PMCPMC12588000

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.