ArticlePLoS computational biology2016
The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review.PLoS pathogens · 2024Pooled it
- Temporal Factors and Missed Doses of Tuberculosis Treatment. A Causal Associations Approach to Analyses of Digital Adherence Data.Annals of the American Thoracic Society · 2020Trial
- Wirelessly observed therapy compared to directly observed therapy to confirm and support tuberculosis treatment adherence: A randomized controlled trial.PLoS medicine · 2019Trial
- A modeling-based framework to evaluate forgiveness of tuberculosis treatment in a BALB/c relapsing mouse model.Antimicrobial agents and chemotherapy · 2026Article
- Risk of rifampicin resistance emergence after incomplete first-line tuberculosis treatment.The European respiratory journal · 2025Article
- Integrating narrative and bibliometric approaches to examine factors and impacts of tuberculosis treatment non-compliance.Multidisciplinary respiratory medicine · 2025Article
- Rifampicin-resistant tuberculosis in Fujian Province, Southeast China: a retrospective analysis of drug resistance screening and treatment outcomes, 2019-2024.Frontiers in public health · 2025Observational
- Unit costs and cost-effectiveness of a device to improve TB treatment adherence in China.IJTLD open · 2024Article
- High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.PLoS computational biology · 2023Article
- FACTORS CONTRIBUTING TO PULMONARY TB TREATMENT LOST TO FOLLOW-UP IN DEVELOPING COUNTRIES: AN OVERVIEW.African journal of infectious diseases · 2023Article
- The risk of drug resistance during long-acting antimicrobial therapy.Proceedings. Biological sciences · 2022Article
- vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding.BMC bioinformatics · 2022Article
- Systematic assessment of clinical and bacteriological markers for tuberculosis reveals discordance and inaccuracy of symptom-based diagnosis for treatment response monitoring.Frontiers in medicine · 2022Article
- Level of and associated factors for non-adherence to anti-tuberculosis treatment among tuberculosis patients in Gamo Gofa zone, southern Ethiopia: cross-sectional study.BMC public health · 2020Article
- Article
- Predictors of recurrent TB in sputum smear and culture positive adults: a prospective cohort study.African health sciences · 2019Article
- Factors influencing completion of treatment among pulmonary tuberculosis patients.Patient preference and adherence · 2019Article
- Insight into treatment of HIV infection from viral dynamics models.Immunological reviews · 2018Review
- Distinct MHC class I-like interacting invariant T cell lineage at the forefront of mycobacterial immunity uncovered inProceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment failure after therapy of pulmonary tuberculosis (TB) infections is an important challenge, especially when it coincides with de novo emergence of multi-drug-resistant TB (MDR-TB). We seek to explore possible causes why MDR-TB has been found to occur much more often in patients with a history of previous treatment. We develop a mathematical model of the replication of Mycobacterium tuberculosis within a patient reflecting the compartments of macrophages, granulomas, and open cavities as well as parameterizing the effects of drugs on the pathogen dynamics in these compartments. We use this model to study the influence of patient adherence to therapy and of common retreatment regimens on treatment outcome. As expected, the simulations show that treatment success increases with increasing adherence. However, treatment occasionally fails even under perfect adherence due to interpatient variability in pharmacological parameters. The risk of generating MDR de novo is highest between 40% and 80% adherence. Importantly, our simulations highlight the double-edged effect of retreatment: On the one hand, the recommended retreatment regimen increases the overall success rate compared to re-treating with the initial regimen. On the other hand, it increases the probability to accumulate more resistant genotypes. We conclude that treatment adherence is a key factor for a positive outcome, and that screening for resistant strains is advisable after treatment failure or relapse.
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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.