Evaluating interferon-gamma release assays for routine screening of health care workers for tuberculosis infection
Notice bibliographique
Résumé
Tuberculosis (TB) continues to pose a global health threat, and was responsible for 1.4 million deaths worldwide in 2010.1 Health care workers (HCWs) are at risk of TB exposure, infection and disease. Effective screening of HCWs for latent TB infection (LTBI) is a critical element of TB control programs in Canada and elsewhere, and requires accurate and reliable tests to diagnose and predict progression to active disease. Recently, novel blood-based assays called interferon-gamma release assays (IGRAs) have been introduced for the diagnosis of LTBI, as an alternative to the tuberculin skin test (TST). IGRAs offer many advantages over the TST, but in the absence of a gold standard for LTBI, their evaluation is problematic. The use of IGRAs for the screening of HCWs remains controversial, and it is unclear how these novel tests can be incorporated into TB infection control programs. The overall objective of this doctoral thesis was to evaluate whether an IGRA (QuantiFERON-TB Gold In-Tube test [QFT]) could be used to identify LTBI in HCWs undergoing routine occupational TB screening in high (India) and low (Canada) TB incidence countries. This manuscript-based thesis includes 4 manuscripts: 1. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review (published in Thorax 2012) 2. TB screening in Canadian health care workers using interferon-gamma release assays (published in PLoS One 2012) 3. Repeat TB screening with interferon-gamma release assays in Canadian health care workers: conversions or unexplained variability? 4. Trajectories of tuberculosis-specific interferon-gamma release assay responses among medical and nursing students in rural IndiaIn the systematic review (manuscript 1), we found a total of 50 published studies that evaluated IGRAs in HCWs. We found large variations in rates of conversions and reversions among serial testing studies in HCWs and little information on their association with TB exposure. Among the cohort of 388 Canadian HCWs (manuscript 2), we found low prevalence of positivity for both TST and QFT, but high rates of unexplained test discordance between TST and QFT. QFT test positivity was not associated with occupational TB exposure in the cross-sectional analysis. Upon repeat, annual screening in Canadian HCWs (manuscript 3), we found high rates of QFT conversions and reversions, which could not be explained by recent TB exposure or treatment. Finally, among the Indian HCW cohort (manuscript 4), we saw high within-person variability in interferon-gamma response over time, that could not be explained by TB exposure, and a high rate of QFT reversions in the absence of treatment. Alternative QFT conversion definitions were evaluated in both the Canadian and Indian cohorts. Alternative definitions estimated reduced rates of QFT conversions, but showed no greater association with TB exposure than the conventional definition. Indian HCWs were classified into patterns of change over time based on interferon-gamma responses, and while 'stable converters' were associated with exposure to TB in the hospital prior to enrolment, the prognosis of HCWs with these 'patterns' remains unclear.Overall, because of the dynamic nature of IGRAs, high rates of conversions and reversions, and the lack of any strong association with recent TB exposure, our data suggest that IGRAs may not be well suited for routine serial testing of HCWs. Their implementation in existing HCW screening programs should be done, if at all, with caution, particularly with respect to the interpretation of conversions and reversions.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,017 | 0,043 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».