Genomic epidemiology links azole-resistant <i>Aspergillus fumigatus</i> hospital bioaerosols to chronic respiratory aspergillosis
Bibliographic record
Abstract
Drug-resistant infections caused by spores of the mould Aspergillus fumigatus pose a major challenge in managing chronic respiratory disease. Evidence shows that a substantial burden of aspergillosis is caused by strains that have evolved resistance to azole antifungal chemicals in the environment, however the contribution of local exposures to the colonisation of patients remains unclear. To investigate routes of acquisition, we whole-genome sequenced A. fumigatus isolates from individuals with chronic pulmonary fungal disease ( n =182, 15 individuals), their homes ( n =101, 10 homes), and hospital environments ( n =102). These data were then integrated with retrospective sequence datasets enabling phylogenetic resolution across 912 genomes of UK A. fumigatus . We found high genetic diversity in clinical isolates, frequent mixed colonisation, and azole resistance in ~25% of infections, particularly in those patients with cystic fibrosis (CF) and chronic pulmonary aspergillosis (CPA). The TR 34 /L98H cyp51A resistance allele, a well characterised marker of environmental adaptation to azole agricultural fungicides, was present in 25% of clinical azole-resistant strains. While azole-resistant A. fumigatus was detected in 6/10 homes, phylogenomic analysis revealed no clear genetic link between the home environment and clinical fungal lung isolates. A. fumigatus was prevalent in hospital environments, with azole-resistant isolates comprising 4.5% ( n =9/202) of air and 3.4% ( n =6/178) of soil isolates, predominantly harbouring the TR 34 /L98H allele. In contrast to homes, phylogenomic and pairwise SNP analysis revealed numerous clinical isolates with >97% genetic identity when compared to those isolated from the hospital environment and randomly chosen pairs of UK isolates. These findings indicate widespread exposure and potential nosocomial acquisition of drug-resistant genotypes of A. fumigatus , supporting the need for targeted environmental surveillance and mitigation of exposures in healthcare settings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".