DOES REDUCED HSV PREVALENCE RESULT IN INCREASED ZOSTER INCIDENCE IN THE US?

项目总结 这一建议汇集了三个观察结果：1)带状疱疹在中国的发病率不断上升 美国，2)HSV-1和HSV-2血清阳性率下降，以及3)发现 单纯疱疹病毒和疱疹病毒之间广泛的T细胞交叉反应。HSV和VZV的致病原因截然不同 疾病，但在作为免疫基础的氨基酸水平上确实有较低程度的序列 交叉反应。人们普遍认为，带状疱疹的风险与VZV呈负相关。 特异性T细胞免疫。我们假设，随着时间的推移，带状疱疹发病率的增加 反映由于单纯疱疹病毒感染率下降而引起的交叉反应免疫下降 感染。我们建议采用嵌套病例对照研究来检验这一假说。我们将测试 来自安慰剂的带状疱疹和匹配对照的参与者的基线样本 带状疱疹预防研究的分支机构。这项先前完成的关于候选带状疱疹的研究 疫苗有一个合适的标本库。我们将确定HSV的血清阳性率是否为 病例组低于对照组。HSV抗体状态将用 华盛顿大学的Western印迹，目前最准确的检测方法。因为有一个 VZV与HSV-1和HSV-2的T细胞高度交叉反应，Western印迹 化验将检测到这两种HSV类型的感染。我们的具体目标是：1)测试 与年龄、性别和健康状况相比，患有带状疱疹的人以前感染HSV的可能性较小。 配对没有带状疱疹的人，以及2)测试在出现带状疱疹的人中， 有单纯疱疹病毒感染者的疾病没有单纯疱疹病毒感染者严重。 血清阴性。功率计算表明，我们将能够检测到HSV的赔率为1.8 用200例带状疱疹患者的血清样本作为对照 目标1控制400次，目标2检测带状疱疹疼痛增加1.4倍的能力为92%。 该项目将阐明艾滋病流行病学的全人口时间变化 一种疱疹病毒对一种与远距离序列相关的病原体的发病率有影响。

PROJECT SUMMARY This proposal brings together three observations: 1) the increasing incidence of zoster in the United States, 2) the decreasing seroprevalence of HSV-1 and HSV-2, and 3) the discovery of extensive T cell cross-reactivity between HSV and VZV. HSV and VZV cause very distinct illnesses, but do share a low degree of sequence at the amino acid level that underlies immune cross-reactivity. It is widely accepted that the risk of zoster is inversely correlated with VZV- specific T cell immunity. We hypothesize that the increasing incidence of zoster over time reflects decreased cross-reactive immunity elicited by HSV, due to decreasing rates of HSV infection. We propose a nested case-control study to examine this hypothesis. We will test baseline samples of participants who developed zoster, and matched controls, from the placebo arm of the Shingles Prevention Study. This previously-completed study of a candidate zoster vaccine has a suitable Specimen Repository. We will determine if the seroprevalence of HSV is lower among cases than among controls. HSV antibody status will be measured with the University of Washington Western blot, the most accurate test available. Because there is a large degree of T cell cross-reactivity between VZV and both HSV-1 and HSV-2, Western blot assays will detect infection with both HSV types. Our Specific Aims are: 1) to test whether persons who develop zoster are less likely to have prior HSV infection than age, sex and health- matched persons without zoster, and 2) to test whether among persons who develop zoster, the disease is less severe among those that have prior HSV infection than those that are HSV seronegative. Power calculations indicate that we will be able to detect a 1.8 odds ratio of HSV infection in the control arm using serum samples from 200 persons that developed zoster and 400 controls for Aim 1, and a 92% power to detect 1.4X increase in zoster pain for Aim 2. This project will shed light on whether the population-wide temporal changes in the epidemiology of one herpesvirus have an impact on the morbidity of a distantly sequence-related pathogen.