Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.
Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.
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DOI：
10.1016/s1473-3099(17)30474-7
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发表时间：
2018-01
期刊：
影响因子：
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通讯作者：
ASTRO-CM Trial Team
中科院分区：
文献类型：
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作者：
Bahr NC;Nuwagira E;Evans EE;Cresswell FV;Bystrom PV;Byamukama A;Bridge SC;Bangdiwala AS;Meya DB;Denkinger CM;Muzoora C;Boulware DR;ASTRO-CM Trial Team
世卫组织建议将Xpert MTB/RIF作为结核性脑膜炎的初始诊断检测。然而，诊断仍然很困难，Xpert的灵敏度约为50-70%，培养的灵敏度约为60%。我们评价了新型Xpert MTB/RIF Ultra（Xpert Ultra）对结核性脑膜炎的诊断性能。我们在乌干达姆巴拉拉的一项治疗HIV相关隐球菌脑膜炎的试验中，前瞻性地获得了诊断性脑脊液（CSF）标本。在姆巴拉拉地区转诊医院对疑似脑膜炎（如头痛、颈项强直、精神状态改变）的HIV感染成人进行连续筛查。我们离心CSF，将沉淀物重悬于2 mL CSF中，并使用分枝杆菌生长指示管培养物检测0.5 mL，使用Xpert检测1 mL，并冷冻保存0.5 mL，随后使用Xpert Ultra检测。我们根据统一的临床病例定义或任何阳性CSF结核试验的复合参考标准评估诊断性能。从2015年2月27日至2016年11月7日，我们前瞻性地评估了129名疑似结核性脑膜炎的HIV感染成人。根据统一的病例定义（不包括Xpert Ultra结果），23名参与者被归类为可能或明确的结核性脑膜炎。Xpert Ultra对可能或明确的结核性脑膜炎的灵敏度为70%（95% CI 47-87; 16/23例），Xpert为43%（23-66; 10/23），培养为43%（23-66; 10/23）。采用复合标准，我们在129名参与者中检测到22例（17%）结核性脑膜炎。Xpert Ultra对结核性脑膜炎的敏感性为95%（95% CI 77-99; 21/22例），高于Xpert（45% [24-68]; 10/22; p= 0.0010）或培养（45% [24-68]; 10/22; p= 0.0034）。在Xpert Ultra检测呈阳性的21名参与者中，13名通过培养、Xpert或两者检测呈阳性，8名仅通过Xpert Ultra检测呈阳性。在这8例患者中，3例被归类为可能的结核性脑膜炎，3例被归类为可能的结核性脑膜炎，2例被归类为非结核性脑膜炎。检测6 mL或更多的CSF与结核病的检出率比小于6 mL相关（26% vs 7%; p= 0.014）。Xpert Ultra检出的结核性脑膜炎显著多于Xpert或培养。世卫组织现在建议使用Xpert Ultra作为疑似结核性脑膜炎的初步诊断检测。国家神经系统疾病和中风研究所，福格蒂国际中心，国家过敏和传染病研究所，英国医学研究理事会/DfID/威康信托全球健康试验，多丽丝杜克慈善基金会。
WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50–70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47–87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23–66; 10/23) for Xpert and 43% (23–66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77–99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24–68]; 10/22; p=0·0010) or culture (45% [24–68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.