Fernando Narmada, Wickremesinghe Shalini, Niloofa Roshan, Rodrigo Chaturaka, Karunanayake Lilani, de Silva H Janaka, Wickremesinghe A R, Premawansa Sunil, Rajapakse Senaka, Handunnetti Shiroma M
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, Sri Lanka.
Tropical Medicine Research Unit, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.
PLoS One. 2016 Jun 9;11(6):e0156085. doi: 10.1371/journal.pone.0156085. eCollection 2016.
Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.
钩端螺旋体病疾病严重程度的发病机制尚不清楚，其原因是病原体的直接损害还是不良免疫反应。关于可用于识别重症患者的氧化应激生物标志物的知识在疾病管理中已显示出巨大价值。因此，本研究的主要目的是评估血清蛋白质和脂质的损伤情况，以及它们作为重症钩端螺旋体病氧化应激生物标志物的意义。在钩端螺旋体病和登革热的地方性流行地区，在登革热流行期间，钩端螺旋体病病例常被误诊为登革热。因此，第二个目的是评估氧化应激标志物在区分重症钩端螺旋体病和登革热危象期的潜力。我们测量了重症钩端螺旋体病患者（n = 60）、轻症钩端螺旋体病患者（n = 50）、登革热危象期患者（n = 30）和健康受试者（n = 30）的血清抗氧化剂（尿酸和胆红素）、总抗氧化能力（AOC）、蛋白质羰基（PC）和脂质过氧化氢（LP）。所有患者组的总抗氧化能力水平相似。然而，尿酸和总胆红素水平显著升高可能反映了重症钩端螺旋体病患者的肾脏和肝脏受累程度（p<0.02）。与登革热危象期感染相比，钩端螺旋体病患者的血清PC和LP水平显著更高（p<0.005）。此外，高血清PC水平似乎可将重症钩端螺旋体病与登革热危象期区分开来[曲线下面积（AUC）= 0.96；p<0.001]。血清PC可能是血清蛋白质氧化损伤的可靠生物标志物，可用于识别重症钩端螺旋体病患者（AUC = 0.99），也可用于区分重症钩端螺旋体病与轻症病例（AUC = 0.78；p<0.005），表明其对发病机制的作用。将血清PC用作钩端螺旋体病严重程度的指标以及在区分钩端螺旋体病与登革热时作为氧化应激生物标志物，将为通过及时的患者管理挽救生命提供机会。
