Universidad Nacional de Asunción, Instituto de Investigaciones en Ciencias de la Salud, San Lorenzo, Paraguay.
Emory University School of Medicine, Division of Infectious Diseases, Atlanta, Georgia, United States of America.
PLoS Negl Trop Dis. 2023 Feb 27;17(2):e0010750. doi: 10.1371/journal.pntd.0010750. eCollection 2023 Feb.
Dengue is the most common vector-borne viral disease worldwide. Most cases are mild, but some evolve into severe dengue (SD), with high lethality. Therefore, it is important to identify biomarkers of severe disease to improve outcomes and judiciously utilize resources.
METHODS/PRINCIPAL FINDINGS: One hundred forty-five confirmed dengue cases (median age, 42; range <1-91 years), enrolled from February 2018 to March 2020, were selected from an ongoing study of suspected arboviral infections in metropolitan Asunción, Paraguay. Cases included dengue virus types 1, 2, and 4, and severity was categorized according to the 2009 World Health Organization guidelines. Testing for anti-dengue virus IgM and IgG and serum biomarkers (lipopolysaccharide binding protein and chymase) was performed on acute-phase sera in plate-based ELISAs; in addition, a multiplex ELISA platform was used to measure anti-dengue virus and anti-Zika virus IgM and IgG. Complete blood counts and chemistries were performed at the discretion of the care team. Age, gender, and pre-existing comorbidities were associated with SD vs. dengue with/without warning signs in logistic regression with odds ratios (ORs) of 1.07 (per year; 95% confidence interval, 1.03, 1.11), 0.20 (female; 0.05,0.77), and 2.09 (presence; 1.26, 3.48) respectively. In binary logistic regression, for every unit increase in anti-DENV IgG in the multiplex platform, odds of SD increased by 2.54 (1.19-5.42). Platelet count, lymphocyte percent, and elevated chymase were associated with SD in a combined logistic regression model with ORs of 0.99 (1,000/μL; 0.98,0.999), 0.92 (%; 0.86,0.98), and 1.17 (mg/mL; 1.03,1.33) respectively.
Multiple, readily available factors were associated with SD in this population. These findings will aid in the early detection of potentially severe dengue cases and inform the development of new prognostics for use in acute-phase and serial samples from dengue cases.
登革热是全球最常见的虫媒病毒病。大多数病例为轻症，但有些会发展为重症登革热（SD），死亡率较高。因此，识别重症疾病的生物标志物对于改善结局和合理利用资源非常重要。
方法/主要发现：本研究从 2018 年 2 月至 2020 年 3 月期间，在巴拉圭首都亚松森正在进行的疑似虫媒病毒感染研究中，选择了 145 例确诊的登革热病例（中位年龄 42 岁；范围 1-91 岁）。病例包括登革热病毒 1、2 和 4 型，根据 2009 年世界卫生组织指南对严重程度进行分类。在平板 ELISA 中对急性期血清进行了抗登革病毒 IgM 和 IgG 以及血清生物标志物（脂多糖结合蛋白和糜酶）检测；此外，还使用多重 ELISA 平台测量了抗登革病毒和抗寨卡病毒 IgM 和 IgG。根据护理团队的判断，进行了全血细胞计数和化学检查。年龄、性别和既往合并症与 logistic 回归分析中的 SD 与有/无警告信号的登革热相关，比值比（OR）分别为 1.07（每年；95%置信区间，1.03，1.11）、0.20（女性；0.05，0.77）和 2.09（存在；1.26，3.48）。在二元 logistic 回归中，多重平台中抗 DENV IgG 每增加一个单位，SD 的可能性增加 2.54（1.19-5.42）。血小板计数、淋巴细胞百分比和升高的糜酶与 SD 相关，在 logistic 回归模型中的比值比（OR）分别为 0.99（1000/μL；0.98，0.999）、0.92（%；0.86，0.98）和 1.17（mg/mL；1.03，1.33）。
本研究人群中，多个易于获得的因素与 SD 相关。这些发现将有助于早期发现潜在的重症登革热病例，并为急性期和登革热病例的系列样本开发新的预后标志物提供信息。
