Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,967
- 试验地点
- 3
- 主要终点
- Diagnostic performance qPCR test in stool samples
研究概览
简要总结
Stool4TB aims to evaluate an innovative stool-based qPCR diagnostic platform (with the capacity to become a POC diagnostic tool) in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the extremely large TB case detection gap by improving TB confirmation rates in children and people living with HIV (PLHIV).
详细描述
Tuberculosis (TB) continues to be a leading cause of morbidity and mortality among children and people living with HIV (PLHIV). Despite significant progress in TB diagnostics, improvement of childhood TB diagnosis continues to be a major challenge and is a key pillar of the WHO "End TB Strategy". TB laboratory confirmation is particularly challenging in children and PLHIV given the difficulty in obtaining sputum samples, and the pauci-bacillary nature of disease. In consequence, bacteriological confirmation of pulmonary TB in young children and immunosuppressed PLHIV remains disappointingly low. Inability to bacteriologically confirm TB, results in both i) under diagnosis which leads to worse outcomes including increased mortality and ii) over or under diagnosis, and poor resource allocation. Given the limitations of currently available sputum-based diagnostic tests in these vulnerable populations, there is a need to develop new tools and identify easy to collect non-respiratory specimens which, combined, could improve bacteriological confirmation. Preliminary data suggest that a new platform, an innovative stool homogenization and DNA isolation method, adds value to existing sputum-based diagnostics by increasing the rates of bacteriological confirmation, and could also be useful as a monitoring tool for treatment response. This platform has the potential to be adapted to a point of care (POC) diagnostic and thus easily implemented in resource-constrained basic health care centres.
Objective: The aim of this project is to evaluate the diagnostic performance of the stool bead-based real-time quantitative PCR (qPCR) platform for TB diagnosis in children and PLHIV. This will be evaluated in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the large TB case detection gap by improving TB confirmation rates in children and PLHIV, while proving feasible and acceptable.
Primary objective:
• Evaluate the diagnostic accuracy of a stool-based real-time quantitative PCR for detecting DNA of Mycobacterium tuberculosis (MTB qPCR), compared to a composite reference standard (sputum and stool Xpert Ultra, sputum culture and urine TB-LAM).
Secondary objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Pediatric Cohort
- •<8 years of age
- •Identified with suspected PTB defined as follows:
- •A child with ≥1 of the following criteria:
- •Persistent unremitting cough (or cough significantly worse than usual in child with chronic lung disease including HIV-related) of >2 weeks duration, unresponsive to a course of appropriate antibiotics (when clinically indicated)
- •Poor growth documented over the preceding 3 months [clear deviation from a previous growth trajectory and/or documented crossing of centile lines in the preceding 3 months and/or; weight-for-age, or weight-for-height Z-score of ≤2 in the absence of information on previous/recent growth trajectory AND not responding to nutritional rehabilitation (or to antiretroviral therapy if HIV-infected)]
- •Persistent unexplained lethargy or reduced playfulness/activity reported by the caregiver.
- •Persistent (>1w) unexplained fever (>38C), reported by a guardian or objectively recorded at least once;
- •In infants 0-60 days, also: unresponsive neonatal pneumonia or unexplained hepatosplenomegaly OR sepsis-like illness (all other more common causes excluded and/or not responding to appropriate therapy/ broad-spectrum antibiotics/antivirals).
- •2) Any duration of cough/ wheeze/ acute pneumonia with ≥1:
- •TB exposure. Either: i) Documented/Reported exposure to a known TB source case (regardless of smear status) in previous 12months OR ii) immunological evidence: positive IGRA or positive TST (defined as >5mm in HIV infected or severely malnourished, >10 otherwise)
- •Chest radiograph suggestive of TB.
- •Adult Cohort (WHO definition of a HIV-positive presumptive TB case)
- •> 15 years of age
- •Confirmed HIV infection (ELISA or molecular)
- •Presenting at any health facility with any of the following: cough, fever, night sweats or unintentional weight loss (any duration).
排除标准
- •Participants will be excluded (both from study groups) if:
- •Receiving TB treatment for >72 hours in previous 2 weeks
- •History of TB treatment in the last year
- •Refusal to provide consent for study participation or HIV testing when status is unknown
- •Severe illness resulting in unstable condition
- •Absolute contra-indication to any of sampling procedures required by the study (ie: acute severe asthma, pertussis syndrome etc.)
研究组 & 干预措施
Adult
Adults >15 with confirmed HIV status and presumptive TB
Pediatric
Children <8 years of age with presumptive TB
结局指标
主要结局
Diagnostic performance qPCR test in stool samples
时间窗: 2 months
Diagnostic performance (Sensitivity, specificity, negative and positive predictive value) of the qPCR test in stool samples with respect to: 1. bacteriologically confirmed tuberculosis as a composite gold standard of any of the other tests positive (including induced sputum and gastric aspirate Xpert Ultra and MGIT culture, stool Ultra or TB-LAM in urine) 2. clinical reference standard case definition (S. Graham et al.; CID 2015).
次要结局
- Comparison of diagnostic performance(2 months)
- Monitor response to TB treatment(6 months)