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Record W4389031359 · doi:10.1093/ofid/ofad500.629

560. Circulating <i>Pneumocystis jirovecii</i> Genotypes in Central-Eastern Canada

2023· article· en· W4389031359 on OpenAlexaffabout
Valérie Roy, Anne E. Desjardins, Simon F. Dufresne, Xavier Marchand-Senécal, Alex Carignan, Philippe J. Dufresne

Bibliographic record

VenueOpen Forum Infectious Diseases · 2023
Typearticle
Languageen
FieldMedicine
TopicPneumocystis jirovecii pneumonia detection and treatment
Canadian institutionsInstitut National de Santé Publique du QuébecCentre hospitalier universitaire de QuébecCentre intégré universitaire de santé et de services sociaux de l'Est-de-l'Île-de-MontréalSte. Anne's HospitalCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalHôpital Maisonneuve-RosemontUniversité de Sherbrooke
FundersModernaPfizer
KeywordsDHPSMultilocus sequence typingGenotypingPneumocystis jiroveciiTypingDihydropteroate synthaseGenotypeMolecular epidemiologyPopulationOutbreakBiologyGeneticsVirologyMedicineHuman immunodeficiency virus (HIV)GeneImmunology

Abstract

fetched live from OpenAlex

Abstract Background Genotyping allows description of Pneumocystis jirovecii (Pjp) heterogenous population structure and clusters linked to nosocomial transmission. It may also reveal mutations associated with resistance to antimicrobials. Recently, a multilocus sequence typing (MLST) scheme by Pasic et al. (2020) has been adopted by International Society for Human & Animal Mycology (ISHAM) as the typing method of choice for this fungus. Methods We analyzed Pjp specimens submitted to the Laboratoire de santé publique du Québec for genotyping between February 2013 and March 2023. The loci genotyped were those used in the Pasic et al. scheme (mt26s, CYB, SOD, B-TUB) with the addition of dihydropteroate synthase (DHPS). Results 296 specimens from Central-Eastern Canada were genotyped: 266 from Quebec, 29 from Ontario, 1 from New Brunswick. Most specimens were submitted as part of outbreak investigations. 187 complete (161 unique and 26 mixed) and 109 incomplete genotypes were obtained. Among specimens with complete and unique genotypes, 87 isolates matched with 23 previously known sequence-types (ST), according to ISHAM MLST scheme. Twenty-four new ST with currently known alleles were described. We also identified 36 isolates with previously undescribed alleles which resulted in 21 new distinct ST. MLST typing allowed epidemiological description of 9 outbreaks. Out of 243 specimens for which DHPS amplification was possible, only one showed a mutation (DHPS 57) previously linked to trimethoprim-sulfamethoxazole resistance. This contrasts with high prevalence of mutant strains seen in some countries. ST-52 was the most prevalent with 32 isolates (20% of strains with complete and unique genotypes) and was involved in 3 outbreaks. A specific CYB mutation (G369T) conferring resistance to atovaquone was uncovered in 18 ST-52 isolates, all associated with an outbreak in one hospital. Conclusion This is the first multicenter study to describe circulating genotypes of Pjp in Central-Eastern Canada. It represents the largest genotyping assembly performed according to the recent ISHAM MLST scheme. We described 45 new ST to be added to ISHAM’s 52 current genotypes. Our study highlights the usefulness of MLST typing in Pjp outbreak investigation and identification of potentially resistant isolates. Disclosures Simon F. Dufresne, MD, AvirPharma Inc.: Grant/Research Support|Merck Canada Inc.: Grant/Research Support Alex Carignan, MD, MSc, GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Moderna: Advisor/Consultant|Moderna: Honoraria|Orimed Pharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria

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 score0.112

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.003
Science and technology studies0.0020.001
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.012
GPT teacher head0.259
Teacher spread0.248 · 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

Citations0
Published2023
Admission routes2
Has abstractyes

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