Can Use of Viral Load Improve Norovirus Clinical Diagnosis and Disease Attribution?
Can Use of Viral Load Improve Norovirus Clinical Diagnosis and Disease Attribution?
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DOI：
10.1093/ofid/ofx131
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发表时间：
2017-06-01
影响因子：
4.2
通讯作者：
Lopman, Benjamin A.
中科院分区：
文献类型：
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作者：
Shioda, Kayoko;Barclay, Leslie;Lopman, Benjamin A.
背景。实时逆转录聚合酶链反应（RT-PCR）是诺如病毒最先进的诊断方法。周期阈值（Ct）是病毒载量的一个指标，可能与症状性疾病以及人口统计学和暴发特征有关。分析了美国和拉丁美洲(1)暴发和散发病例以及(2)无症状控制的数据。通过多变量回归模型，我们评估了各种因素与Ct值之间的关系，并计算了症状存在和诺如病毒归因部分的比值比（ORs）。进行了受体操作特征分析，以确定确定致病感染的最佳Ct截止点。与无症状对照组（28.5 +/- 1.4）相比，有症状病例的周期阈值较低（即病毒载量较高）（模型校正平均+/-标准误差：25.3 +/- 1.2）。周期阈值在不同年龄组、诺如病毒基因组、标本采集时间、爆发环境和传播模式之间存在显著差异。基因组II (GII) Ct值与症状存在相关（OR = 1.1），使我们能够估计16%的腹泻病可归因于诺如病毒。优化后的Ct截断值对基因I组和基因I组的敏感性和特异性较差。周期阈值与宿主、病原体和爆发因素有关。周期阈值可能不能有效区分个别患者的致病感染，但它们对于旨在确定疾病属性的流行病学研究是有用的。
Background. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the state-of-the-art diagnostic for norovirus. Cycle threshold (Ct), an indicator of viral load, may be associated with symptomatic disease as well as demographic and outbreak characteristics.Methods. Data on (1) outbreak and sporadic cases and (2) asymptomatic controls in the United States and Latin America were analyzed. With multivariate regression models, we assessed relationships between various factors and Ct values, and we calculated odds ratios (ORs) for the presence of symptoms and attributable fractions of norovirus. Receiver-operating characteristic analysis was performed to define an optimal Ct cutoff to identify disease-causing infections.Results. Cycle threshold values were lower (ie, higher viral loads) among symptomatic cases (model-adjusted mean +/- standard error: 25.3 +/- 1.2) compared with asymptomatic controls (28.5 +/- 1.4). Cycle threshold values were significantly different across age groups, norovirus genogroups, timing of specimen collection, outbreak settings, and transmission modes. Genogroup II (GII) Ct values were associated with presence of symptoms (OR = 1.1), allowing us to estimate that 16% of diarrheal disease was attributable to norovirus. The optimized Ct cutoff led to poor sensitivity and specificity for genogroup I and GII.Conclusions. Cycle threshold values were associated with host, pathogen, and outbreak factors. Cycle threshold values may not effectively distinguish disease-causing infection for individual patients, but they are useful for epidemiological studies aiming to attribute disease.