Haruhiko Ishioka, Aniruddha Ghose, Hugh W Kingston, Katherine Plewes, Stije J Leopold, Ketsanee Srinamon, Prakaykaew Charunwatthana, Maswood Ahmed, A K M Shamsul Alam, Anita Tuip-de Boer, Md Amir Hossain, Arjen M Dondorp, Marcus J Schultz
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Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.</p><p><strong>Results: </strong>Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (r<sub>s</sub> = 0.39; P = 0.004, r<sub>s</sub> = 0.43; P = 0.001, r<sub>s</sub> = 0.54; P < 0.001, r<sub>s</sub> = 0.44; P < 0.001, r<sub>s</sub> = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (r<sub>s</sub> = 0.37; P = 0.005, r<sub>s</sub> = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.</p><p><strong>Conclusions: </strong>IL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"320"},"PeriodicalIF":2.4000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515577/pdf/","citationCount":"0","resultStr":"{\"title\":\"The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study.\",\"authors\":\"Haruhiko Ishioka, Aniruddha Ghose, Hugh W Kingston, Katherine Plewes, Stije J Leopold, Ketsanee Srinamon, Prakaykaew Charunwatthana, Maswood Ahmed, A K M Shamsul Alam, Anita Tuip-de Boer, Md Amir Hossain, Arjen M Dondorp, Marcus J Schultz\",\"doi\":\"10.1186/s12936-024-05142-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. 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Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.</p><p><strong>Results: </strong>Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (r<sub>s</sub> = 0.39; P = 0.004, r<sub>s</sub> = 0.43; P = 0.001, r<sub>s</sub> = 0.54; P < 0.001, r<sub>s</sub> = 0.44; P < 0.001, r<sub>s</sub> = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (r<sub>s</sub> = 0.37; P = 0.005, r<sub>s</sub> = 0.47; P < 0.001, respectively). 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引用次数: 0
摘要
背景：肺水肿是重症疟疾的一种可怕且难以预测的并发症，可在开始抗疟治疗后出现。前炎症介质被认为在其发病机制中起着核心作用：方法：我们在孟加拉国的两家医院开展了一项探索性研究，以评估生物标志物对重症恶性疟原虫疟疾患者出现临床肺水肿的预测能力。研究人员将患者入院时血浆中白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子（TNF）、可溶性高级糖化终产物受体（sRAGE）、表面活性蛋白-D（SP-D）、会厌细胞分泌蛋白（CC16）和克雷布斯-冯登肺素-6（KL-6）的浓度与健康对照组进行了比较。评估了这些生物标志物与血浆乳酸和恶性疟原虫富组氨酸蛋白 2（PfHRP2）水平之间的相关性。构建了接收者操作特征曲线（ROC），以评估相关生物标志物对临床肺水肿的预测能力：在 106 名接受筛查的恶性疟原虫疟疾患者中，56 人被归类为重症疟疾，死亡率为 29%。9名患者（16%）入院后出现临床肺水肿。与健康对照组相比，患者血浆中相关生物标志物的水平较高。IL-6、IL-8、TNF、sRAGE和CC16水平与血浆PfHRP2水平密切相关（rs = 0.39; P = 0.004, rs = 0.43; P = 0.001, rs = 0.54; P s = 0.44; P s = 0.43; P = 0.001）。此外，IL-6 和 IL-8 水平与血浆乳酸水平也有很好的相关性（rs = 0.37；P = 0.005，rs = 0.47；P 结论：IL-6、IL-8、TNF-6 和 TNF-8 水平与血浆乳酸水平有很好的相关性：IL-6、IL-8、TNF、sRAGE、SP-D、CC16 和 KL-6 不能用于预测重症疟疾患者的临床肺水肿。
The predictive capacity of biomarkers for clinical pulmonary oedema in patients with severe falciparum malaria is low: a prospective observational study.
Background: Pulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.
Methods: An exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and Plasmodium falciparum histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.
Results: Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (rs = 0.39; P = 0.004, rs = 0.43; P = 0.001, rs = 0.54; P < 0.001, rs = 0.44; P < 0.001, rs = 0.43; P = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (rs = 0.37; P = 0.005, rs = 0.47; P < 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.
Conclusions: IL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.
期刊介绍：
Malaria Journal is aimed at the scientific community interested in malaria in its broadest sense. It is the only journal that publishes exclusively articles on malaria and, as such, it aims to bring together knowledge from the different specialities involved in this very broad discipline, from the bench to the bedside and to the field.
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