Plasma superoxide dismutase-1 as a surrogate marker of vivax malaria severity.
Plasma superoxide dismutase-1 as a surrogate marker of vivax malaria severity.
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DOI：
10.1371/journal.pntd.0000650
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发表时间：
2010-04-06
影响因子：
3.8
通讯作者：
Barral-Netto M
中科院分区：
文献类型：
--
作者：
Andrade BB;Reis-Filho A;Souza-Neto SM;Raffaele-Netto I;Camargo LM;Barral A;Barral-Netto M
恶性疟原虫和间日疟原虫感染的严重后果已被描述。确定敏感和可靠的疾病严重程度标志是改善患者护理的基础。在疟疾中存在强烈的促炎反应，伴随着氧化应激和产生活性氧物种。炎性细胞因子如肿瘤坏死因子-α和抗氧化剂如超氧化物歧化酶-1可能是疾病严重程度的候选生物标志物。在这里，我们测试了血浆中的SOD-1水平是否可以作为严重间日疟的生物标志物。血浆样本来自巴西亚马逊地区的居民，具有传播间日疟原虫的高风险。疟疾诊断采用镜检和套式聚合酶链式反应两种方法。共纳入219人：非感染志愿者(n = 90人)和间日疟患者(n = 60人)，轻度(n = 50人)和重度感染(n = 19人)。SOD-1与寄生虫血症、血肌酐和丙氨酸氨基转移酶水平直接相关，而肿瘤坏死因子-α仅与后者相关。比较超氧化物歧化酶-1和肿瘤坏死因子-α水平对病情的预测能力。在预测间日疟严重程度方面，SOD-1蛋白水平比肿瘤坏死因子-α更有效。在鉴别轻度感染方面，升高的超氧化物歧化酶-1水平比肿瘤坏死因子-α显示出更高的敏感性(分别为76%和30%；p<；0.0001)和更高的特异性(100%和97%；p<；0.0001)。在预测严重间日疟时，超氧化物歧化酶-1水平比肿瘤坏死因子-α显示出更高的敏感性(分别为80%和56%；p<；0.0001；似然比：7.45vs.3.14；p<；0.0001)。SOD-1和TNF-α均不能区分间日疟原虫感染和恶性疟原虫感染。在具有不同间日疟临床表现的个体中，超氧化物歧化酶-1是一种强大的疾病严重程度预测因子。尽管间日疟原虫被认为是一种相对良性的疾病，但由于治疗失败或卫生保健不足，间日疟原虫感染与致命后果有关。确定敏感和可靠的疾病严重程度标志物对于提高患者护理质量非常重要。虽然不是必须的，但一个好的标记物应该与疾病的发病机制有密切的因果关系。在急性疟疾期间，人们注意到强烈的炎症反应和有据可查的氧化爆发。在释放的自由基中，超氧阴离子占绝大多数。本研究旨在评估使用一种负责清除超氧阴离子的抗氧化酶作为间日疟严重程度的标志的可靠性。因此，我们调查了亚马逊地区高度流行间日疟的个体，目的是通过测量血浆超氧化物歧化酶-1(SOD-1)水平来预测感染严重程度。此外，我们还比较了超氧化物歧化酶-1和肿瘤坏死因子-α的预测能力。在有不同间日疟临床表现的个体中，超氧化物歧化酶-1比肿瘤坏死因子-α更能预测疾病的严重性。这一发现为严重间日疟病例的初步筛查开辟了新的途径。
Severe outcomes have been described for both Plasmodium falciparum and P. vivax infections. The identification of sensitive and reliable markers of disease severity is fundamental to improving patient care. An intense pro-inflammatory response with oxidative stress and production of reactive oxygen species is present in malaria. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and antioxidant agents such as superoxide dismutase-1 (SOD-1) are likely candidate biomarkers for disease severity. Here we tested whether plasma levels of SOD-1 could serve as a biomarker of severe vivax malaria. Plasma samples were obtained from residents of the Brazilian Amazon with a high risk for P. vivax transmission. Malaria diagnosis was made by both microscopy and nested PCR. A total of 219 individuals were enrolled: non-infected volunteers (n = 90) and individuals with vivax malaria: asymptomatic (n = 60), mild (n = 50) and severe infection (n = 19). SOD-1 was directly associated with parasitaemia, plasma creatinine and alanine amino-transaminase levels, while TNF-alpha correlated only with the later enzyme. The predictive power of SOD-1 and TNF-alpha levels was compared. SOD-1 protein levels were more effective at predicting vivax malaria severity than TNF-alpha. For discrimination of mild infection, elevated SOD-1 levels showed greater sensitivity than TNF-alpha (76% vs. 30% respectively; p<0.0001), with higher specificity (100% vs. 97%; p<0.0001). In predicting severe vivax malaria, SOD-1 levels exhibited higher sensitivity than TNF-alpha (80% vs. 56%, respectively; p<0.0001; likelihood ratio: 7.45 vs. 3.14; p<0.0001). Neither SOD-1 nor TNF-alpha could discriminate P. vivax infections from those caused by P. falciparum. SOD-1 is a powerful predictor of disease severity in individuals with different clinical presentations of vivax malaria. Despite being considered a relatively benign disease, Plasmodium vivax infection has been associated with fatal outcomes due to treatment failure or inadequate health care. The identification of sensitive and reliable markers of disease severity is important to improve the quality of patient care. Although not imperative, a good marker should have a close causative relationship with the disease pathogenesis. During acute malaria, an intense inflammatory response and a well-documented oxidative burst are noted. Among the free radicals released, superoxide anions account for the great majority. The present study aimed to evaluate the reliability of using an antioxidant enzyme, responsible for the clearance of superoxide anions, as a marker of vivax malaria severity. Thus, we investigated individuals from an Amazonian region highly endemic for vivax malaria with the goal of predicting infection severity by measuring superoxide dismutase-1 (SOD-1) plasma levels. In addition, we compared the predictive power SOD-1 to that of the tumor necrosis factor (TNF)-alpha. SOD-1 was a more powerful predictor of disease severity than TNF-alpha in individuals with different clinical presentations of vivax malaria. This finding opens up new approaches in the initial screening of severe vivax malaria cases.
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影响因子：
5.9
作者：
KERN, P;HEMMER, CJ;DIETRICH, M
通讯作者：
DIETRICH, M
影响因子：
3
作者：
Andrade, Bruno Bezerril;Rocha, Bruno Coelho;Barral-Netto, Manoel
通讯作者：
Barral-Netto, Manoel
影响因子：
3.8
作者：
Dive, D;Gratepanche, S;Khalife, J
通讯作者：
Khalife, J
影响因子：
15.8
作者：
Genton B;D'Acremont V;Rare L;Baea K;Reeder JC;Alpers MP;Müller I
通讯作者：
Müller I
影响因子：
4.4
作者：
Khouri, Ricardo;Bafica, Andre;Van Weyenbergh, Johan
通讯作者：
Van Weyenbergh, Johan