Nuove strategie per la valutazione della persistenza dei bacilli vitali nella tubercolosi latente e attiva (TB-LIVE)
Current diagnostic tools such as interferon gamma release assay (IGRA) and purified protein derivative (PPD) can not distinguish patients with latent tuberculosis infection (LTBI) and persistence of live mycobacteria. This inability to rule out living mycobacteria in patients investigated for LTBI leads to unnecessary and potentially harmful treatment regimes all around the globe.
The goal of this observational study is to identify candidate biomarkers for viable bacilli in latent tuberculosis in order to decrease the use of unnecessary and ineffective antibiotic treatment.
Panoramica dello studio
Stato
Descrizione dettagliata
Tuberculosis (TB) is the second leading cause of death due to a single infectious agent, with the main burden in resource-limited settings and in vulnerable populations. It is estimated that approximately 25% of the global population is infected with TB. LTBI is a condition where the mycobacteria rests within the body instead of creating active disease. About half of the active TB cases develop within 2 years of exposure and the other half reactivates as distant as several decades post exposure. Persistence of viable bacilli is a prerequisite for the reactivation of TB.
Through sampling of peripheral blood the investigators will investigate how selected cytokines, enzyme activity and gene expression changes during course of treatment, 4-6 months, and during follow up, 1 year. These patterns will be compared to the patterns of patients with: latent TB without treatment, active TB with treatment as well as healthy controls. Samples will be drawn at 0, 1, 6 and 12 months, after treatment initialization when applicable. Healthy controls will only be sampled once. Most of the analysis will be performed on TB-antigen stimulated blood.
The investigators hypothesize that there is a substantial fraction of latent TB patients who do not harbor live mycobacteria and that this is reflected in study outcome measures when given treatment. Furthermore, the investigators hypothesize that this fraction of latent TB patients will resemble healthy controls in terms of outcome measures whereas their counterpart, latent TB patients harboring living bacteria, will not.
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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Skåne County
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Malmö, Skåne County, Svezia, 20502
- Skåne University Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
Individuals 15 years or older diagnosed with latent- or active tuberculosis or found healthy as part of routine care at the out- and inpatient department of the department for infectious diseases at Skåne University Hospital in Malmö, Sweden
Descrizione
LTBI (2 groups)
Inclusion Criteria:
- latent tuberculosis: Interferon gamma (IFN-γ) >0.70 IU/ml in the Quantiferon-TB Plus assay
- age 15-25 years OR high likelihood of recent TB transmission
- informed consent
Exclusion Criteria:
- active tuberculosis
- chronic illness
- immunosuppressive treatment
- pregnancy (including 6 months post-partum)
- previous treatment for either active or latent TB infection
Controls
Inclusion Criteria:
- age 15-25 years
- informed consent
Exclusion Criteria:
- latent- OR active tuberculosis
- chronic illness
- immunosuppressive treatment
- pregnancy (including 6 months post-partum)
- previous treatment for either active or latent TB infection
Active TB
Inclusion Criteria:
- diagnosed with active TB
- informed consent
Exclusion Criteria:
age < 15 years
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: COHORT
- Prospettive temporali: PROSPECTIVE
Coorti e interventi
Gruppo / Coorte |
|---|
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Latent TB on treatment
Treatment according to existing Swedish guidelines with: Oral rifampicin 10 mg/kg (max 600mg) once daily during 4 months OR Oral isoniazide 5 mg/kg (max 300mg) once daily in combination with 40mg vitamin B6 (pyridoxin) during 6 months |
|
Latent TB not on treatment
Latent TB without indication for treatment OR patient who do not want to receive treatment |
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Active TB with treatment
Treatment according to existing Swedish guidelines. Duration and choice of antibiotic therapy depending on the condition. |
|
Healthy control
Healthy |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Cytokine levels
Lasso di tempo: 0-12 months
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To determine levels of selected cytokines in supernatants of Mtb-incubated whole blood obtained from persons diagnosed with LTBI during the course of treatment, and to identify patterns of cytokine expression suggestive of bacterial eradication. |
0-12 months
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|
Gene expression
Lasso di tempo: 0-12 months
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To characterize patterns of small non-coding RNA (sncRNA) expression (including microRNAs) in blood and plasma from persons diagnosed with LTBI, and to identify patterns of sncRNA expression in individuals with LTBI suggestive of bacterial eradication. |
0-12 months
|
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Activity of indoleamine 2, 3-dioxygenase (IDO)
Lasso di tempo: 0-12 months
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3. To characterize IDO activity in plasma from persons diagnosed with LTBI, and to determine whether changes in IDO activity during the course of LTBI reflect bacterial eradication |
0-12 months
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Per Björkman, Professor, Lund University, Faculty of Medicine, Department of Translational Medicine
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Infezione latente
- Processi patologici
- Attributi della malattia
- Infezioni
- Infezioni batteriche Gram-positive
- Infezioni batteriche
- Infezioni batteriche e micosi
- Infezioni da actinomiceti
- Infezioni da micobatteri
- Tubercolosi
- Condizioni patologiche, segni e sintomi
- Infezione persistente
- Tubercolosi latente
Altri numeri di identificazione dello studio
- 2021-04885
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
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