Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients.
Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients.
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DOI：
10.1172/jci140461
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发表时间：
2020-11-02
期刊：
影响因子：
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通讯作者：
Denkinger CM
中科院分区：
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作者：
Broger T;Nicol MP;Sigal GB;Gotuzzo E;Zimmer AJ;Surtie S;Caceres-Nakiche T;Mantsoki A;Reipold EI;Székely R;Tsionsky M;van Heerden J;Plisova T;Chikamatsu K;Lowary TL;Pinter A;Mitarai S;Moreau E;Schumacher SG;Denkinger CM
结核病诊断不充分是减轻疾病负担的一个主要障碍，迫切需要准确的即时检测。我们评估了fujifilp SILVAMP TB lipoarabinmanannan (FujiLAM) POCT对hiv阴性门诊患者结核病诊断的准确性，并将其与Alere确定TB LAM Ag (AlereLAM) POCT和基于实验室的超灵敏电化学发光LAM研究测定（EclLAM）进行比较。在这项多中心诊断测试准确性研究中，我们招募了秘鲁和南非门诊医疗中心出现肺结核症状的hiv阴性成人。使用FujiLAM、AlereLAM和EclLAM检测尿样，并根据微生物参考标准（MRS）和复合参考标准评估诊断准确性。纳入372名艾滋病毒阴性参与者，微生物证实的结核病患病率为30%。与MRS相比，AlereLAM、FujiLAM和EclLAM的敏感性分别为10.8%（95%可信区间[CI] 6.3% ~ 18.0%）、53.2% （95% CI 43.9% ~ 62.1%）和66.7% （95% CI 57.5% ~ 74.7%）。AlereLAM、FujiLAM和EclLAM的特异性分别为92.3% （95% CI 88.5% ~ 95.0%）、98.9% （95% CI 96.7% ~ 99.6%）和98.1% （95% CI 95.6% ~ 99.2%）。AlereLAM、FujiLAM和EclLAM的阳性似然比分别为1.4、46.2和34.8，阳性预测值分别为37.5%、95.2%和93.7%。与AlereLAM相比，FujiLAM在艾滋病毒阴性参与者中检测出的结核病患者数量是AlereLAM的5倍，具有很高的阳性预测值，并且有可能改善在护理点对结核病的快速诊断。EclLAM证明了额外的灵敏度增益是可能的，这突出了LAM作为生物标志物的潜力。需要进一步的研究来评估FujiLAM在前瞻性队列中的表现、成本效益及其在实际临床环境中的影响。全球健康创新技术基金、英国国际发展部、荷兰外交部、比尔和梅林达·盖茨基金会、澳大利亚外交和贸易部、德国联邦教育和研究部（通过德国信贷机构）、美国国立卫生研究院和国家过敏和传染病研究所。
Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM). In this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard. Three hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%–18.0%), 53.2% (95% CI 43.9%–62.1%), and 66.7% (95% CI 57.5%–74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%–95.0%), 98.9% (95% CI 96.7%–99.6%), and 98.1% (95% CI 95.6%–99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively. Compared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM’s potential as a biomarker. Additional research is required to assess FujiLAM’s performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings. Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.