Observational studyThe Lancet. Respiratory medicine2013
Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study.
Observational study in The Lancet. Respiratory medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00864383 (A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen), which is not on this map. Cited by 109 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis
Who cites it
109 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark.The Lancet. Microbe · 2021Pooled it
- Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review.Frontiers in genetics · 2020Pooled it
- Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review.BMC medicine · 2016Pooled it
- Towards culture-free sequencing of Mycobacterium tuberculosis: evaluating new targeted and whole-genome approaches for genotyping and drug resistance profiling.Genome medicine · 2026Trial
- Treatment and recurrence on re-treatment tuberculosis patients: a randomized clinical trial and 7-year perspective cohort study in China.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Trial
- Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.The New England journal of medicine · 2014Trial
- Whole genome sequencing for Mycobacterium tuberculosis in public health responses: a review of current practice and enablers in select low-incidence jurisdictions.BMC public health · 2026Review
- Host response biomarkers of tuberculosis recurrence and treatment failure.Communications medicine · 2026Article
- Transmission dynamics and attributable burden of tuberculosis among young and middle-aged adults in urban Shanghai: a genomic epidemiology study.Frontiers in public health · 2026Article
- Article
- Characterizing the Etiology of Recurrent Tuberculosis Using Whole Genome Sequencing: Alaska, 2008-2020.The Journal of infectious diseases · 2025Article
- Molecular typing of Mycobacterium tuberculosis: a review of current methods, databases, softwares, and analytical tools.FEMS microbiology reviews · 2025Review
- Ouabain alleviatesFrontiers in immunology · 2025Article
- Endogenous reactivation cases identified by whole genome sequencing ofJournal of clinical tuberculosis and other mycobacterial diseases · 2024Article
- Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis.Nature communications · 2024Article
- Timing of recurrence after treatment of pulmonary TB.IJTLD open · 2024Article
- Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles.The Lancet. Microbe · 2024Review
- Recurrent Pulmonary Tuberculosis in China, 2005 to 2021.JAMA network open · 2024Article
- Article
- Unraveling tuberculosis patient cluster transmission chains: integrating WGS-based network with clinical and epidemiological insights.Frontiers in public health · 2024Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
backgroundRecurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.
methodsWe assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.
findingsWe assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.
interpretationWhole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.
fundingWellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.
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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.