잠복 및 활동성 결핵에서 생존 가능한 간균의 지속성 평가를 위한 새로운 전략 (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.
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
연락처 및 위치
연구 장소
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Skåne County
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Malmö, Skåne County, 스웨덴, 20502
- Skåne University Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
샘플링 방법
연구 인구
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
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 관찰 모델: COHORT
- 시간 관점: PROSPECTIVE
코호트 및 개입
그룹/코호트 |
|---|
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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 |
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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 |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Cytokine levels
기간: 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
기간: 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)
기간: 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
|
공동 작업자 및 조사자
스폰서
수사관
- 수석 연구원: Per Björkman, Professor, Lund University, Faculty of Medicine, Department of Translational Medicine
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2021-04885
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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