粪便Xpert MTB/RIF Ultra检测HIV感染者中结核分枝杆菌的性能：一项多中心前瞻性诊断研究。
Performance of stool Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis among adults living with HIV: a multicentre, prospective diagnostic study.
作者信息
Kasule George W, Hermans Sabine, Acacio Sozinho, Kay Alexander, Nsubuga Joachim Kikoyo, Fernández-Escobar Carlos, Shiba Nosisa, Carratalá-Castro Lucia, Semugenze Derrick, Mwachan Patricia, Munguambe Shilzia, Ehrlich Joanna, Lopez-Varela Elisa, DiNardo Andrew R, Cobelens Frank, Lange Christoph, Joloba Moses, Mandalakas Anna M, Ssengooba Willy, García-Basteiro Alberto L
机构信息
Department of Medical Microbiology, College of Health Sciences Makerere University, Kampala, Uganda; Universitat de Barcelona, Barcelona Institute for Global Health, Hospital Clínic, Barcelona, Spain; National TB Reference Laboratory, Ministry of Health, Kampala, Uganda.
Amsterdam UMC, location University of Amsterdam, Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands; Centre for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam UMC, location University of Amsterdam, Amsterdam Public Health-Global Health, Amsterdam Institute for Immunity and Infectious Diseases, Amsterdam, Netherlands.
出版信息
Lancet Microbe. 2025 Jul;6(7):101085. doi: 10.1016/j.lanmic.2025.101085. Epub 2025 Apr 4.
BACKGROUND
When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.
METHODS
This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic tests (urine tuberculosis biomarker-based lateral-flow lipoarabinomannan [TB-LAM], sputum Ultra, and sputum culture), and stratified by CD4 cell count. We compared sputum versus stool Ultra performance against a composite reference standard of TB-LAM and sputum culture (CMRS2). We also calculated the diagnostic yield among all tested. This study is registered with ClinicalTrials.gov, NCT05047315.
FINDINGS
Between Dec 2, 2021, and Aug 14, 2024, 677 participants were enrolled (247 [36%] men and 430 [64%] women). Tuberculosis was microbiologically confirmed in 119 participants by the CMRS: 39 (33%) had a positive test with sputum Ultra, 30 (25%) had a positive test with culture, and 84 (71%) had a positive test with urine TB-LAM. The sensitivity of stool Ultra compared with CMRS was 23·7% (28/118 [95% CI 16·4-32·4]) and the specificity was 94·0% (504/536 [91·7-95·9]). The sensitivity of stool Ultra in participants with CD4 counts less than or equal to 200 cells per μL was 45·5% (10/22 [24·4-67·8]) compared with 21·3% (17/80 [12·9-31·8]) in those with CD4 counts greater than 200 cells per μL. Against the CMRS2, we observed no differences in sensitivity between sputum and stool Ultra on the basis of CD4 cell count. Stool Ultra resulted in additional cases detected of 23% (30/133) compared with sputum Ultra, 29% (38/133) compared with sputum culture, and 33% (44/133) compared with TB-LAM. The overall diagnostic yield for all treated for stool Ultra was 9% (60/677), for TB-LAM was 12% (84/677), for sputum Ultra was 6% (39/677), and for sputum culture was 4% (30/677).
INTERPRETATION
These results suggest stool Ultra could be used as an additional test for tuberculosis diagnosis among people with HIV, particularly among those with CD4 counts less than 200 cells per μL.
FUNDING
EDCTP2 and EDCTP3 Programmes supported by the EU.
背景
感染艾滋病毒的人患肺结核时，痰涂片显微镜检查往往显示未检测到抗酸杆菌。我们旨在评估粪便Xpert MTB/RIF Ultra（以下简称Ultra）在艾滋病毒感染成人中检测结核分枝杆菌的诊断准确性。
方法
这项多中心、前瞻性诊断准确性研究在斯威士兰、莫桑比克和乌干达的门诊和住院健康中心进行。我们纳入了15岁及以上患有艾滋病毒且疑似患有结核病的成年人。我们使用简单的一步处理方法，针对包括三项世界卫生组织推荐的结核病诊断测试（基于尿液结核生物标志物的侧向流动脂阿拉伯甘露聚糖[TB-LAM]、痰Ultra和痰培养）的综合微生物学参考标准（CMRS），评估粪便Ultra的诊断准确性，并按CD4细胞计数分层。我们将痰与粪便Ultra针对TB-LAM和痰培养的综合参考标准（CMRS2）的性能进行了比较。我们还计算了所有检测者的诊断率。本研究已在ClinicalTrials.gov注册，注册号为NCT05047315。
结果
在2021年12月2日至2024年8月14日期间，共纳入677名参与者（247名[36%]男性和430名[64%]女性）。CMRS在119名参与者中微生物学确诊了结核病：39名（33%）痰Ultra检测呈阳性，30名（25%）培养检测呈阳性，84名（71%）尿液TB-LAM检测呈阳性。与CMRS相比，粪便Ultra的敏感性为23.7%（28/118[95%CI 16.4 - 32.4]），特异性为94.0%（504/536[91.7 - 95.9]）。CD4细胞计数小于或等于200个/μL的参与者中，粪便Ultra的敏感性为45.5%（10/22[24.4 - 67.8]），而CD4细胞计数大于200个/μL的参与者中为21.3%（17/80[12.9 - 31.8]）。针对CMRS2，我们观察到基于CD4细胞计数，痰和粪便Ultra的敏感性没有差异。与痰Ultra相比，粪便Ultra额外检测出23%（30/133）的病例，与痰培养相比为29%（38/133），与TB-LAM相比为33%（44/133）。粪便Ultra的总体诊断率为9%（60/677），TB-LAM为12%（84/677），痰Ultra为6%（39/677），痰培养为4%（30/677）。
解读
这些结果表明，粪便Ultra可作为艾滋病毒感染者结核病诊断的补充检测方法，特别是在CD4细胞计数小于200个/μL的人群中。
资助
由欧盟支持的EDCTP2和EDCTP3计划。
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