Nicholson Karl G, Abrams Keith R, Batham Sally, Medina Marie Jo, Warren Fiona C, Barer Mike, Bermingham Alison, Clark Tristan W, Latimer Nicholas, Fraser Maria, Perera Nelun, Rajakumar K, Zambon Maria
Infectious Diseases Unit, Vaccine Evaluation Centre, University Hospitals of Leicester NHS Trust and Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Department of Health Sciences, University of Leicester, Leicester Medical School, Leicester, UK.
Health Technol Assess. 2014 May;18(36):1-274, vii-viii. doi: 10.3310/hta18360.
Western industrialised nations face a large increase in the number of older people. People over the age of 60 years account for almost half of the 16.8 million hospital admissions in England from 2009 to 2010. During 2009-10, respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days.
To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza, respiratory syncytial virus (RSV) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture.
We carried out a randomised controlled trial (RCT) to evaluate impact on prescribing and clinical outcomes of point-of-care tests (POCTs) for influenza A and B and pneumococcal infection, reverse transcriptase-polymerase chain reaction (RT-PCR) tests for influenza A and B and RSV A and B, and conventional culture for these pathogens. We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection, RT-PCR for influenza and sputum culture for S. pneumoniae using samples collected during the RCT. We did a systematic review and meta-analysis of POCTs for influenza A and B. We evaluated ease and speed of use of each test, process outcomes and cost-effectiveness.
There was no evidence of association between diagnostic group and prescribing or clinical outcomes. Using PCR as 'gold standard', Quidel Influenza A + B POCT detected 24.4% [95% confidence interval (CI) 16.0% to 34.6%] of influenza infections (specificity 99.7%, 95% CI 99.2% to 99.9%); viral culture detected 21.6% (95% CI 13.5% to 31.6%; specificity 99.8%, 95% CI 99.4% to 100%). Using blood culture as 'gold standard', BinaxNOW pneumococcal POCT detected 57.1% (95% CI 18.4% to 90.1%) of pneumococcal infections (specificity 92.5%; 95% CI 90.6% to 94.1%); sputum culture detected 100% (95% CI 2.5% to 100%; specificity 97.2%, 95% CI 94.3% to 98.9%). Overall, pooled estimates of sensitivity and specificity of POCTs for influenza from the literature were 74% (95% CI 67% to 80%) and 99% (95% CI 98% to 99%), respectively. Median intervals from specimen collection to test result were 15 minutes [interquartile range (IQR) 10-23 minutes) for Quidel Influenza A + B POCT, 20 minutes (IQR 15-30 minutes) for BinaxNOW pneumococcal POCT, 50.8 hours (IQR 44.3-92.6 hours) for semi-nested conventional PCR, 29.2 hours (IQR 26-46.9 hours) for real-time PCR, 629.6 hours (IQR 262.5-846.7 hours) for culture of influenza and 84.4 hours (IQR 70.7-137.8 hours) and 71.4 hours (IQR 69.15-84.0 hours) for culture of S. pneumoniae in blood and sputum, respectively. Both POCTs were rated straightforward and undemanding; blood culture was moderately complex and all other tests were complex. Costs and quality-adjusted life-years (QALYs) of each diagnostic strategy were similar. Incrementally, PCR was most cost-effective (78.3% probability at a willingness to pay of £20,000/QALY). Few patients were admitted within a timescale conducive to treatment with a neuraminidase inhibitor according to National Institute for Health and Care Excellence guidance.
The accuracy study was limited by inadequate gold standards.
All tests had limitations. We found no evidence that POCTs for influenza or S. pneumoniae, or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes. The total costs and QALYs of each diagnostic strategy were similar, although, incrementally, PCR was the most cost-effective strategy. The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions, but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR.
Current Controlled Trials ISRCTN21521552.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 36. See the NIHR Journals Library website for further project information.
西方工业化国家面临老年人口数量大幅增加的情况。在2009年至2010年英格兰的1680万例住院病例中，60岁以上的人群占了近一半。在2009 - 10年期间，呼吸道感染约占30分之一的住院病例以及5150万个住院日中的20分之一。
与传统实验室培养方法相比，确定用于流感、呼吸道合胞病毒（RSV）和肺炎链球菌感染的快速分子及即时诊断检测的诊断准确性、临床有效性和成本效益。
我们进行了一项随机对照试验（RCT），以评估针对甲型和乙型流感及肺炎球菌感染的即时检测（POCT）、针对甲型和乙型流感以及甲型和乙型RSV的逆转录聚合酶链反应（RT-PCR）检测以及针对这些病原体的传统培养方法对处方和临床结果的影响。我们使用在RCT期间收集的样本评估了POCT对流感和肺炎球菌感染的诊断准确性、RT-PCR对流感的诊断准确性以及痰培养对肺炎链球菌的诊断准确性。我们对甲型和乙型流感的POCT进行了系统评价和荟萃分析。我们评估了每种检测方法的使用便捷性和速度、过程结果以及成本效益。
没有证据表明诊断组与处方或临床结果之间存在关联。以PCR作为“金标准”，Quidel甲型 + 乙型流感POCT检测出24.4%[95%置信区间（CI）16.0%至34.6%]的流感感染（特异性99.7%，95%CI 99.2%至99.9%）；病毒培养检测出21.6%（95%CI 13.5%至31.6%；特异性99.8%，95%CI 99.4%至100%）。以血培养作为“金标准”，BinaxNOW肺炎球菌POCT检测出57.1%（95%CI 18.4%至90.1%）的肺炎球菌感染（特异性92.5%；95%CI 90.6%至94.1%）；痰培养检测出100%（95%CI 2.5%至100%；特异性97.2%，95%CI 94.3%至98.9%）。总体而言，文献中POCT对流感的敏感性和特异性汇总估计分别为74%（95%CI 67%至80%）和99%（95%CI 98%至99%）。从标本采集到检测结果的中位间隔时间，Quidel甲型 + 乙型流感POCT为15分钟[四分位间距（IQR）10 - 23分钟]，BinaxNOW肺炎球菌POCT为20分钟（IQR 15 - 30分钟），半巢式常规PCR为50.8小时（IQR 44.3 - 92.6小时），实时PCR为29.2小时（IQR 26 - 46.9小时），流感培养为629.6小时（IQR 262.5 - 846.7小时），血和痰中肺炎链球菌培养分别为84.4小时（IQR 70.7 - 137.8小时）和71.4小时（IQR 69.15 - 84.0小时）。两种POCT都被评为操作简单且要求不高；血培养中等复杂，所有其他检测都很复杂。每种诊断策略的成本和质量调整生命年（QALY）相似。逐步来看，PCR最具成本效益（在支付意愿为20,000英镑/QALY时概率为78.
