Evidence map›Paper›PMID 41239519›Full record

Observational studyGenome medicine2025

Clinical and bacterial determinants of unfavorable tuberculosis treatment outcomes: an observational study in Georgia.

Galo A Goig, Chloé Loiseau, Nino Maghradze, Kakha Mchedlishvili, Teona Avaliani, Ana Tsutsunava, Daniela Brites, Sevda Kalkan, Sonia Borrell, Rusudan Aspindzelashvili and 5 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

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

3 citing papers in PubMed.

  1. Within-host evolution of drug tolerance inJAC-antimicrobial resistance · 2026
    Article
  2. Observational
  3. 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

15 authors.

Galo A GoigSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland. galo.goig@swisstph.ch.
Chloé LoiseauSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Nino MaghradzeSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Kakha MchedlishviliSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Teona AvalianiNational Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.
Ana TsutsunavaNational Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.
Daniela BritesSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Sevda KalkanSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Sonia BorrellSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Rusudan AspindzelashviliNational Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.
Zaza AvalianiNational Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.
Maia KipianiNational Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.
Nestani TukvadzeSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Levan JugheliSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.
Sebastien GagneuxSwiss Tropical and Public Health Institute, Kreuzstrasse 2, Allschwil, 4123, Switzerland.

Funding

Emory-Georgia TB Research Training ProgramD43TW007124 · FIC · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Nestani Tukvadze · 2004 to 2026
$4.6M
FIC NIH HHS D43 TW007124HORIZON EUROPE European Research Council 883582-ECOEVODRTBSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 320030-227432
6 · The paper itself

Abstract

backgroundTuberculosis (TB) remains a major public health concern. Improving TB control programs and treatment success requires a deeper understanding of the factors that determine disease presentation and treatment outcomes. While the importance of patient factors is well established, our understanding of the bacterial determinants of disease presentation and treatment outcomes in TB remains limited.

methodsIn this study, we analyzed the Mycobacterium tuberculosis complex (MTBC) genomes and the associated clinical data from 4529 TB patients in the country of Georgia covering a period of 13 years. We used multivariable modeling together with genome-wide association studies (GWAS) to identify patient and bacterial factors that determine TB disease manifestation and clinical outcomes.

resultsMultivariable modelling confirmed the role of demographic and clinical factors in determining treatment outcomes, as well as the efficacy of novel TB treatments containing bedaquiline. In addition, we found that several bacterial factors, including the MTBC lineage, the specific mutations conferring resistance to rifampicin and fluoroquinolones, as well as a high bacterial burden, were associated with unfavorable outcomes. GWAS analyses revealed no bacterial genetic mutations associated with treatment outcomes beyond the known drug resistance-conferring mutations. However, we found that mutations in the bacterial gene sufD were linked to a reduced risk of lung cavities and a lower bacterial burden within patients. By contrast, specific mutations conferring resistance to rifampicin and fitness compensatory mutations were associated with a higher bacterial burden.

conclusionsOur results show that both patient and bacterial factors determine disease presentation and clinical outcomes in TB. They also support the rationale of optimizing treatment regimens against drug-resistant TB with existing drugs based on the specific genetic features of the pathogen. Finally, our results highlight sufD as a possible therapeutic candidate.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisTuberculosisAdultAgedDrug Resistance, BacterialFemaleGenome, BacterialGenome-Wide Association StudyGeorgia (Republic)HumansMaleMiddle AgedMutationTreatment OutcomeAntitubercular AgentsAntimicrobial resistanceGenomicsGWASPrecision medicineTreatment outcomesTuberculosis

Identifiers

PMID41239519
PMCPMC12619330

What OpenQuestion holds

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Registered trials

None linked

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.