Observational studyEBioMedicine2020
Dynamics of within-host Mycobacterium tuberculosis diversity and heteroresistance during treatment.
Observational study in EBioMedicine, 2020. 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 58 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- In Host Mutational Adaptation of Mycobacterium Tuberculosis Complex Strains During Tuberculosis Infection.The Journal of infectious diseases · 2026Pooled it
- ClinicalFrontiers in microbiology · 2025Pooled it
- Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review.Frontiers in genetics · 2020Pooled it
- Can Diagnostic Delay Amplify Drug Resistance in Tuberculosis? A Critical Integrative Reflection on Bacterial Adaptation, Persistence, Within-Host Evolution, and Heteroresistance.Diseases (Basel, Switzerland) · 2026Article
- Population-level genome sequencing reveals distinctmSystems · 2026Article
- Population-level genome sequencing reveals distinct Mycobacterium tuberculosis intrahost mutational trajectories in simian immunodeficiency virus co-infected and antiretroviral treated non-human primates.bioRxiv : the preprint server for biology · 2026Article
- Divergent Evolution of Tuberculosis Lesions During Treatment: A Longitudinal CT-Based Analysis of Progression and Regression Patterns.Diagnostics (Basel, Switzerland) · 2026Article
- Benchmarking within-sample minority variant detection with short-read sequencing inbioRxiv : the preprint server for biology · 2026Article
- Heteroresistance inFrontiers in cellular and infection microbiology · 2026Review
- Performance evaluation of mNGS in pathogen diagnosis of skin and soft tissue infections and its optimization effect on antibiotic decision-making.Frontiers in cellular and infection microbiology · 2026Article
- Genetic diversity ofGut microbes · 2025Article
- Mixed infections and heteroresistance ofEmerging microbes & infections · 2025Article
- Clinical and bacterial determinants of unfavorable tuberculosis treatment outcomes: an observational study in Georgia.Genome medicine · 2025Observational
- The applications and advantages of nanopore sequencing in bacterial antimicrobial resistance surveillance and research.npj antimicrobials and resistance · 2025Review
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Unpacking bedaquiline heteroresistance: the importance of intermediate profiles for phenotypic drug susceptibility testing.Antimicrobial agents and chemotherapy · 2025Article
- Within-host bacterial evolution and the emergence of pathogenicity.Nature microbiology · 2025Review
- Dissecting rifampicin heteroresistance inJournal of medical microbiology · 2025Article
- South Asian origin and global transmission history ofmSystems · 2025Article
- Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps inMicroorganisms · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundStudying within-host genetic diversity of Mycobacterium tuberculosis (Mtb) in patients during treatment may identify adaptations to antibiotic and immune pressure. Understanding the significance of genetic heteroresistance, and more specifically heterozygous resistance-associated variants (RAVs), is clinically important given increasing use of rapid molecular tests and whole genome sequencing (WGS).
methodsWe analyse data from six studies in KwaZulu-Natal, South Africa. Most patients (>75%) had baseline rifampicin resistance. Sputum was collected for culture at baseline and at between two and nine intervals until month six. Positive cultures underwent WGS. Mixed infections and reinfections were excluded from analysis.
findingsBaseline Mtb overall genetic diversity (at treatment initiation or major change to regimen) was associated with cavitary disease, not taking antiretroviral therapy if HIV infected, infection with lineage 2 strains and absence of second-line drug resistance on univariate analyses. Baseline genetic diversity was not associated with six-month outcome. Genetic diversity increased from baseline to weeks one and two before returning to previous levels. Baseline genetic heteroresistance was most common for bedaquiline (6/10 [60%] of isolates with RAVs) and fluoroquinolones (9/62 [13%]). Most patients with heterozygous RAVs on WGS with sequential isolates available demonstrated RAV persistence or fixation (17/20, 85%). New RAVs emerged in 9/286 (3%) patients during treatment. We could detect low-frequency RAVs preceding emergent resistance in only one case, although validation of deep sequencing to detect rare variants is required.
interpretationIn this study of single-strain Mtb infections, baseline within-host bacterial genetic diversity did not predict outcome but may reveal adaptations to host and drug pressures. Predicting emergent resistance from low-frequency RAVs requires further work to separate transient from consequential mutations.
fundingWellcome Trust, NIH/NIAID.
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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.