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Record W3177683961 · doi:10.1101/2021.06.30.21259748

Phylogeography and transmission of <i>M. tuberculosis</i> in Moldova

2021· preprint· en· W3177683961 on OpenAlexaff
Chongguang Yang, Benjamin Sobkowiak, Vijay Naidu, Alexandru Codreanu, Nelly Ciobanu, Kenneth S. Gunasekera, Melanie H. Chitwood, Sofia Alexandru, Stela Bivol, Marcus Russi, Joshua Havumaki, Patrick Cudahy, Heather Fosburgh, Christopher J. Allender, David M. Engelthaler, Nicolas A. Menzies, Joshua L. Warren, Valeriu Crudu, Caroline Colijn, Ted Cohen

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldMedicine
TopicTuberculosis Research and Epidemiology
Canadian institutionsSimon Fraser University
Fundersnot available
KeywordsCladeTuberculosisTransmission (telecommunications)Drug resistanceLineage (genetic)Mycobacterium tuberculosisPhylogenetic treeMultiple drug resistanceBiologyIncidence (geometry)Molecular epidemiologyVirologyCluster (spacecraft)Evolutionary biologyDemographyGeneticsMedicineGenotypeGenePathology

Abstract

fetched live from OpenAlex

Abstract Background The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously-treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible TB, is the main driver of incident MDR-TB in these countries. Methods We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of M. tuberculosis . Results Of 2236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. 92% of MDR M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified three large clades that were comprised nearly uniformly of MDR-TB; two of these clades were of Beijing lineage and one of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity. Conclusions The MDR-TB epidemic in Moldova is the result of local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.030

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.311
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuemedRxiv→Same topicTuberculosis Research and Epidemiology→French-language works237,207→