Nuevas estrategias para la evaluación de la persistencia de bacilos viables en tuberculosis latente y activa (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.
Descripción general del estudio
Estado
Descripción detallada
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 de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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Skåne County
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Malmö, Skåne County, Suecia, 20502
- Skåne University Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
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
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
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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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Cytokine levels
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Per Björkman, Professor, Lund University, Faculty of Medicine, Department of Translational Medicine
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Infección latente
- Procesos Patológicos
- Atributos de la enfermedad
- Infecciones
- Infecciones por bacterias grampositivas
- Infecciones bacterianas
- Infecciones bacterianas y micosis
- Infecciones por Actinomycetales
- Infecciones por micobacterias
- Tuberculosis
- Condiciones Patológicas, Signos y Síntomas
- Infección persistente
- Tuberculosis latente
Otros números de identificación del estudio
- 2021-04885
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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