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Abstract：
BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.
METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS).
RESULTS: The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1).
CONCLUSIONS: In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum.
BACKGROUND: National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.
METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS).
RESULTS: The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1).
CONCLUSIONS: In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum.
BACKGROUND: National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.
摘要：
背景：尽管在高负担环境中诊断结核病的快速分子检测越来越多，许多结核病患者未被诊断。依赖痰作为结核病诊断的主要标本有助于这种诊断差距。我们评估了一种新型粪便定量PCR（qPCR）检测方法在非洲三个结核病负担较高的国家中诊断结核病的诊断准确性和累加产量。
方法：我们在Eswatini进行了一项前瞻性诊断准确性研究，莫桑比克,2020年9月21日至2023年2月2日，坦桑尼亚将新型粪便qPCR检测对结核病的诊断准确性与当前痰和粪便中结核分枝杆菌DNA检测的诊断标准进行比较，Xpert-MTB/RIFUltra(XpertUltra)。痰,凳子,尿液样本由一群参与者提供，10岁或以上，诊断为肺结核。结核病（病例）的参与者在临床诊断或实验室确认后的结核病治疗开始后72小时内招募。没有结核病的参与者（对照组）包括在6个月随访期间未发展为结核病的病例的家庭接触者。将该性能与稳健的复合微生物参考标准(CMRS)进行比较。
结果：青少年和成人队列（n=408）包括268名确诊或临床结核病（病例）的参与者，其中147人（55%）携带艾滋病毒，和140名没有结核病的参与者（对照）。与在结核分枝杆菌培养上可检测到生长的参与者相比，新型粪便qPCR的灵敏度为93·7％（95％CI87·4-97·4），与痰XpertUltra相比，为88·1%（81·3-93·0）。粪便qPCR具有与痰XpertUltra相当的灵敏度(94·8%，89·1-98·1）与文化相比。与CMRS相比，粪便qPCR的敏感性高于目前对粪便结核病诊断的标准，XpertUltra(80·4%，73·4-86·2vs73·5%，66·0-80·1；配对比较时p=0·025）。与痰XpertUltra或痰培养相比，qPCR还鉴定出17-21％的额外结核病例。在没有结核病的对照组中，粪便qPCR的特异性为96·9％（92·2-99·1）。
结论：在这项研究中，从粪便标本中诊断结核病的新型qPCR在青少年和成人中的准确性高于目前的粪便诊断PCR金标准，Xpert-MTB/RIFUltra,以及对痰液的Xpert-MTB/RIFUltra的同等敏感性。
背景：美国国立卫生研究院（NIH）过敏和传染病，和美国国立卫生研究院福格蒂国际中心。
方法：我们在Eswatini进行了一项前瞻性诊断准确性研究，莫桑比克,2020年9月21日至2023年2月2日，坦桑尼亚将新型粪便qPCR检测对结核病的诊断准确性与当前痰和粪便中结核分枝杆菌DNA检测的诊断标准进行比较，Xpert-MTB/RIFUltra(XpertUltra)。痰,凳子,尿液样本由一群参与者提供，10岁或以上，诊断为肺结核。结核病（病例）的参与者在临床诊断或实验室确认后的结核病治疗开始后72小时内招募。没有结核病的参与者（对照组）包括在6个月随访期间未发展为结核病的病例的家庭接触者。将该性能与稳健的复合微生物参考标准(CMRS)进行比较。
结果：青少年和成人队列（n=408）包括268名确诊或临床结核病（病例）的参与者，其中147人（55%）携带艾滋病毒，和140名没有结核病的参与者（对照）。与在结核分枝杆菌培养上可检测到生长的参与者相比，新型粪便qPCR的灵敏度为93·7％（95％CI87·4-97·4），与痰XpertUltra相比，为88·1%（81·3-93·0）。粪便qPCR具有与痰XpertUltra相当的灵敏度(94·8%，89·1-98·1）与文化相比。与CMRS相比，粪便qPCR的敏感性高于目前对粪便结核病诊断的标准，XpertUltra(80·4%，73·4-86·2vs73·5%，66·0-80·1；配对比较时p=0·025）。与痰XpertUltra或痰培养相比，qPCR还鉴定出17-21％的额外结核病例。在没有结核病的对照组中，粪便qPCR的特异性为96·9％（92·2-99·1）。
结论：在这项研究中，从粪便标本中诊断结核病的新型qPCR在青少年和成人中的准确性高于目前的粪便诊断PCR金标准，Xpert-MTB/RIFUltra,以及对痰液的Xpert-MTB/RIFUltra的同等敏感性。
背景：美国国立卫生研究院（NIH）过敏和传染病，和美国国立卫生研究院福格蒂国际中心。
