Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB
Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB
复制标题
DOI：
10.1136/thoraxjnl-2015-207999
复制
发表时间：
2016-09-01
期刊：
影响因子：
10
通讯作者：
Walzl, Gerhard
中科院分区：
文献类型：
--
作者：
Chegou, Novel N.;Sutherland, Jayne S.;Walzl, Gerhard
在资源有限的环境中，迫切需要使用方便、快速、廉价但准确的结核病诊断工具。我们调查的主机生物标志物检测血清样本中获得的成年人的体征和症状提示结核病在初级保健诊所在五个非洲国家（马拉维，纳米比亚，南非，冈比亚和乌干达），结核病diseases.Methods的诊断，我们前瞻性地招募个人提出的症状，肺结核调查，结核病评估之前。我们使用多重细胞因子平台评估了储存的血清样品中的22种宿主蛋白质生物标志物。使用一个预先建立的诊断算法，包括实验室，临床和放射学检查结果，参与者被分类为明确的TB，可能的TB，可疑的TB状态或非肺TB。结果在716名参与者中，185人明确，29人可能的TB病例，6可疑的TB疾病状态，而487没有证据的TB。在训练样本集（n=491）上鉴定的C反应蛋白、甲状腺素运载蛋白、IFN-γ、补体因子H、载脂蛋白-A1、诱导蛋白10和血清淀粉样蛋白A的七种标志物生物特征，在测试集（n=210）中诊断TB疾病，灵敏度为93.8%。（95% CI 84.0%-98.0%），特异性73.3%（95% CI 65.2%至80.1%），阳性和阴性预测值为60.6%（95% CI 50.3%至70.1%）和96.4%（95% CI 90.5%至98.8%），无论艾滋病毒感染状况或研究地点。结论我们已经确定了七个-用于诊断结核病的标记宿主血清蛋白生物特征，而不考虑非洲的HIV感染状况或种族。这些结果为开发肺结核现场友好的床旁筛查试验提供了希望。
Background User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease.Methods We prospectively enrolled individuals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum samples using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB.Results Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training sample set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site.Conclusions We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB.