Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy

BackgroundMany patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation.MethodsWe assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed.ResultsChanges in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients.ConclusionsMonitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation.研究背景 在中低收入国家，许多接受结核病（TB，tuberculosis）治疗的患者是基于临床疑似诊断开展治疗的，并未获得细菌学确诊。这一现状往往源于缺乏快速、简便且精准的诊断工具，以及医护人员对现有检测方法预测价值的信心不足。我们此前曾在结核病动物模型中报道，宿主标志物水平会在治疗启动后快速发生变化。 研究方法 本研究评估了结核病患者在治疗最初两周内的宿主生物标志物动力学特征，以此识别对治疗产生应答的患者。研究共纳入经临床确诊并接受结核病治疗的成年患者：尼日利亚29例，尼泊尔24例，均进行了相关分析。 研究结果 抗结核治疗第一周后，非特异性宿主生物标志物（尤其是IP-10）的浓度变化与结核病的细菌学确诊结果显著相关。在治疗第0天至第7天期间，IP-10水平下降超过300pg/ml的患者中，可识别出75%的涂片阳性及涂片阴性的培养阳性患者，且可准确排除全部9例培养阴性患者的结核病诊断。 研究结论 监测IP-10对治疗的早期应答反应，可作为一种简化检测方法的基础，同时有助于识别被临床误诊为结核病的患者，或是正在接受不当治疗的耐药菌株感染者。我们认为该方法尤其适用于难以确诊的患者，例如涂片阴性的HIV阳性患者，或是常未获得细菌学确诊即接受治疗的肺外结核病患者。