Lawn Stephen D, Kerkhoff Andrew D, Burton Rosie, Schutz Charlotte, Boulle Andrew, Vogt Monica, Gupta-Wright Ankur, Nicol Mark P, Meintjes Graeme
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
BMC Med. 2017 Mar 21;15(1):67. doi: 10.1186/s12916-017-0822-8.
We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB.
Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions.
Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9-99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50-11.75).
Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.
我们之前报道过，在一家南非地区医院因病情需住院治疗的HIV阳性成年人中，三分之一的患者经实验室确诊患有结核病（TB），并且通过对入院第一天采集的浓缩尿样进行Xpert MTB/RIF检测，几乎三分之二的病例能够得到快速诊断。采用基于尿液的常规即时检验结核筛查是一项颇具吸引力的干预措施，使用简单、低成本的诊断工具（如用于HIV相关结核病的Determine TB-LAM侧向流动快速检测）可能会推动该措施的实施。
在一家南非乡镇医院，于HIV阳性成年患者入院后24小时内系统采集痰液、尿液和血液样本。根据临床指征，在住院期间采集额外的临床样本。结核病的定义为使用Xpert MTB/RIF或液体培养在任何样本中检测到结核分枝杆菌。确定尿液脂阿拉伯甘露聚糖（LAM）检测的诊断率、准确性和预后价值，但尿液LAM检测结果不影响治疗决策。
纳入连续427例未接受过结核病治疗的HIV阳性成年急性病住院患者，无论其临床表现或症状如何。139例患者被诊断为结核病（结核病患病率32.6%；CD4细胞计数中位数为80个/μL）。入院后的头24小时内，37.0%的患者采集了痰液（即时和/或诱导痰液）样本，99.5%的患者采集了尿液样本（P<0.001）。这些样本的诊断率分别为：痰液显微镜检查19.4%（n=27/139），痰液Xpert检测26.6%（n=37/139），尿液LAM检测38.1%（n=53/139），痰液Xpert/尿液LAM联合检测52.5%（n=73/139）（P<0.01）。CD4细胞计数<100个/μL的患者相应的诊断率分别为18.9%、24.3%、55.4%和63.5%（P<0.01）。尿液LAM检测的诊断率与呼吸道症状无关，LAM检测的特异性（采用二级临界值）为98.9%（274/277；95%置信区间[CI]96.9-99.8）。在结核病病例中，尿液LAM检测呈阳性与90天死亡率密切相关（调整后的风险比为4.20；95%CI 1.50-11.75）。
对于新入院的HIV阳性成年人，使用Determine TB-LAM检测尿液进行结核病常规检测，与痰液检测联合使用时可大幅提高诊断率，且特异性极高，对于无呼吸道结核病症状和/或无法咳痰的患者具有重要作用。该检测还能快速识别预后不良的个体。
