University of Puerto Rico, UPR- Comprehensive Cancer Center(UPRCCC), Division of Cancer Biology, San Juan, Puerto Rico.
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
PLoS Negl Trop Dis. 2020 Jan 29;14(1):e0007971. doi: 10.1371/journal.pntd.0007971. eCollection 2020 Jan.
Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study.
Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity.
Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course.
While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.
登革热是一种重要的虫媒病毒病，每年约有 1 亿例登革热病例，其中约 5%导致重症疾病。临床上很难将登革热与其他急性发热性疾病（AFI）区分开来，而且诊断性血液检测费用昂贵。我们评估了尿液中抗 DENV IgM 用于识别临床研究中 AFI 患者登革热病例的效用。
2012 年 5 月至 2013 年 3 月，共纳入 1538 例发热≤7 天的研究参与者，采集病史并采集血清和尿液标本。血清检测 DENV RNA 和抗 DENV IgM。尿液检测抗 DENV IgM，并计算其检测血清实验室阳性登革热病例的灵敏度和特异性。我们评估了在疾病病程中早期（发病后≤5 天[DPO]）和晚期（6-14 DPO）尿液抗 DENV IgM 阳性与登革热严重程度的关系。
与血清抗 DENV IgM ELISA 结果相比，尿液抗 DENV IgM 的灵敏度和特异性分别为 47.4%和 98.5%，与血清 rRT-PCR 结果相比分别为 29.7%和 91.1%。尿液抗 DENV IgM 阳性与患者性别或既往慢性疾病无关。在疾病病程早期，与无预警症状者相比，出现预警症状的登革热患者尿液中抗 DENV IgM 的比例显著更高（20.4% vs. 4.3%）。在疾病病程晚期，严重程度组之间尿液抗 DENV IgM 阳性的比例无差异。
尽管尿液抗 DENV IgM 的检测缺乏足够的诊断灵敏度，但它是实验室阳性登革热的高度特异性标志物，其在疾病早期的存在可能区分更严重的疾病。进一步评估 DPO 尿液抗 DENV IgM 以确定其作为登革热早期诊断（和可能的预后）标志物的效用是必要的。
