Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity

Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity
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DOI:
10.1371/journal.pntd.0001244
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发表时间:
2011-07-01
影响因子:
3.8
通讯作者:
Buchy, Philippe
Buchy, Philippe
中科院分区:
医学2区
文献类型:
--
作者:
Duong, Veasna;Ly, Sowath;Buchy, Philippe

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背景:在急性感染中检测登革热NS1抗原可用于登革热的早期诊断。这项研究的目的是评估影响Platelia NS1抗原试剂盒(BioRad)性能的临床和病毒学因素,并评估NS1抗原和登革热病毒载量作为登革热严重程度标志物的潜在用途。方法/主要研究结果:血液样本来自柬埔寨2006年和2007年登革热流行期间在磅湛医院住院的患者。在接受检测的214名家庭成员中,243名有症状的患者和17名无症状的个人被确认感染登革热。Platelia NS1抗原试剂盒的总敏感性为57.5%,特异性为100%。NS1抗原联合IgM抗体捕获ELISA检测可显著提高登革热诊断的敏感性。DHF/DSS患者NS1抗原阳性率显著高于DHF/DSS患者,原发感染患者显著高于继发感染患者,病毒血症(>5log/mL)患者和DENV-1感染患者NS1抗原阳性率显著高于DHF/DSS患者。在无症状个体中,NS1抗原捕获敏感性往往低于有症状患者。结论:NS1抗原检测试剂盒在不同形式的登革热感染或疾病中的总体敏感性有很大差异。在发烧后3天内采集样本的患者,在原感染、DENV-1感染、病毒血症水平较高的患者以及DF而不是DHF/DSS患者中,敏感性最高。在无症状患者中,RT-PCR检测已被证明比NS1抗原检测更敏感。NS1抗原水平与病毒血症显著相关,NS1抗原比例低与病情加重有关。
Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad) and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity.Methodology/Principal Findings: Blood specimens were collected from patients hospitalized at the Kampong Cham hospital during the 2006 and 2007 dengue epidemics in Cambodia. Dengue infection was confirmed in 243/339 symptomatic patients and in 17 asymptomatic individuals out of 214 household members tested. Overall sensitivity and specificity of Platelia NS1 Ag kit were 57.5% and 100% respectively. NS1 Ag assay combined with IgM antibody capture ELISA significantly increased the sensitivity for dengue diagnosis. NS1 Ag positivity rate was found significantly higher in DF than in DHF/DSS, in primary than in secondary infections, in patients with a high viremia (>5 log/mL) and in patients infected with DENV-1. In asymptomatic individuals, the NS1 Ag capture sensitivity tends to be lower than that in symptomatic patients. Milder disease severity was observed independently in patients with RNA copy number >5 log10 cDNA equivalents/mL or in high level of NS1 antigen ratio or in DENV-1 infection.Conclusions: Overall sensitivity of NS1 Ag detection kit varied widely across the various forms of dengue infection or disease. Sensitivity was highest in patients sampled during the first 3 days after onset of fever, in patients with primary infection, DENV-1 infection, with high level of viremia and in DF rather than DHF/DSS. In asymptomatic patients, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. The NS1 antigen level correlated significantly with viremia and a low NS1 antigen ratio was associated with more severe disease.