Aprahamian Hrayer, Bish Douglas R, Bish Ebru K
Grado Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, VA, U.S.A..
Grado Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, VA, U.S.A.
Stat Med. 2016 Dec 10;35(28):5283-5301. doi: 10.1002/sim.7066. Epub 2016 Aug 2.
An accurate estimation of the residual risk of transfusion-transmittable infections (TTIs), which includes the human immunodeficiency virus (HIV), hepatitis B and C viruses (HBV, HCV), among others, is essential, as it provides the basis for blood screening assay selection. While the highly sensitive nucleic acid testing (NAT) technology has recently become available, it is highly costly. As a result, in most countries, including the United States, the current practice for human immunodeficiency virus, hepatitis B virus, hepatitis C virus screening in donated blood is to use pooled NAT. Pooling substantially reduces the number of tests required, especially for TTIs with low prevalence rates. However, pooling also reduces the test's sensitivity, because the viral load of an infected sample might be diluted by the other samples in the pool to the point that it is not detectable by NAT, leading to potential TTIs. Infection-free blood may also be falsely discarded, resulting in wasted blood. We derive expressions for the residual risk, expected number of tests, and expected amount of blood wasted for various two-stage pooled testing schemes, including Dorfman-type and array-based testing, considering infection progression, infectivity of the blood unit, and imperfect tests under the dilution effect and measurement errors. We then calibrate our model using published data and perform a case study. Our study offers key insights on how pooled NAT, used within different testing schemes, contributes to the safety and cost of blood. Copyright © 2016 John Wiley & Sons, Ltd.
准确估计输血传播感染（TTIs）的残余风险至关重要，输血传播感染包括人类免疫缺陷病毒（HIV）、乙型和丙型肝炎病毒（HBV、HCV）等，因为它为血液筛查检测方法的选择提供了依据。虽然高灵敏度核酸检测（NAT）技术最近已经可用，但成本高昂。因此，在包括美国在内的大多数国家，目前对献血中人类免疫缺陷病毒、乙型肝炎病毒、丙型肝炎病毒筛查的做法是使用混合NAT。混合检测大大减少了所需的检测数量，尤其是对于患病率较低的输血传播感染。然而，混合检测也会降低检测的灵敏度，因为感染样本的病毒载量可能会被混合中的其他样本稀释到NAT无法检测到的程度，从而导致潜在的输血传播感染。无感染的血液也可能被错误丢弃，造成血液浪费。考虑到感染进展、血液单位的传染性以及在稀释效应和测量误差下的不完美检测，我们推导了各种两阶段混合检测方案（包括 Dorfman 型检测和基于阵列的检测）的残余风险、预期检测次数和预期血液浪费量的表达式。然后，我们使用已发表的数据校准模型并进行案例研究。我们的研究提供了关于在不同检测方案中使用混合NAT如何影响血液安全性和成本的关键见解。版权所有© 2016 John Wiley & Sons, Ltd.
