The Utility of Interferon-Gamma Release Assays in TB-HIV co-infected Children

描述（由申请人提供）：我们项目的主要目标是改善患有人类免疫缺陷病毒-1（HIV）和结核分枝杆菌（M。tb）通过准确识别感染M. TB.该研究旨在检查干扰素-γ释放试验（IGRA）在结核分枝杆菌和HIV合并感染儿童中的实用性和解释。关于使用IGRA检测M的数据有限。HIV感染儿童的结核病感染/在结核病（TB）和HIV高度流行的环境中进行的一项前瞻性社区研究中，将在5岁以下HIV感染（N=300）和未感染（N=500）儿童中解决以下具体目标：1）评估传统结核菌素皮肤试验（TST）和IGRA之间的一致性，2）评估TST和IGRA在M的标准梯度上的性能。肺结核暴露，3）测量潜在的相互作用和混杂变量的影响和4）确定随时间改变儿童对TST和IGRA反应的因素。我们将利用一项以社区为基础的结核病控制家庭接触研究设计，通过结核分枝杆菌暴露的标准化梯度（接触评分）来描述家庭和社区结核分枝杆菌暴露和感染。标准化的M.结核病接触得分将是指示病例传染性以及儿童与结核病指示病例接触的接近程度和持续时间的综合衡量标准。将收集一组集中的年龄、营养和HIV相关免疫状态（CD 4 T淋巴细胞计数）标准化指标，以全面评估其对TST和IGRA的影响。纵向分析还将衡量其他修饰因素的影响，包括自暴露以来的时间、抗逆转录病毒治疗、艾滋病毒病毒载量和异烟肼治疗。该研究涉及原始数据收集，将解决我们目前关于IGRA检测M的实用性和具体适用性的知识中的重要空白。艾滋病病毒感染儿童的结核病感染。这包括确定最佳的截止值的解释IGRA在艾滋病毒感染和未感染的儿童在高度流行的设置。在艾滋病毒感染的儿童中，那些最容易受到结核病相关发病率和死亡率影响的IGRA可能有助于通过准确和及时的诊断和有针对性的预防或治疗来进行最佳的临床管理。准确的诊断工具也将限制过度诊断和治疗。因此，IGRA在改善结核病控制和减少儿童艾滋病毒-结核病相关疾病和死亡方面具有巨大潜力。铺设说明：新型干扰素γ释放测定法在改善结核病控制和减少儿童艾滋病毒-结核病相关疾病和死亡方面具有巨大潜力。然而，必须在结核病和艾滋病毒高负担环境中的艾滋病毒感染儿童中研究这些检测的实用性和解释。

DESCRIPTION (provided by applicant): The principal objective of our project is to improve the health of children with Human Immunodeficiency Virus-1 (HIV) and Mycobacterium tuberculosis (M. tb) co-infection by accurately identifying those infected with M. tb. The study was designed to examine the utility and interpretation of Interferon-Gamma Release Assays (IGRA) in children with M.tb and HIV co-infection. There are limited data on the use of IGRA to detect M. tb infection in HIV-infected children/In a prospective community-based study in a setting highly endemic for tuberculosis (TB) and HIV, the following specific aims will be addressed in HIV-infected (N=300) and uninfected (N=500) children ¿5 years of age: 1) asses the agreement between the traditional tuberculin skin test (TST) and IGRAs, 2) assess the performance of the TST and IGRAs across a standard gradient of M. tb exposure, 3) measure the impact of potential interaction and confounding variables and 4) identify factors that modify children's response to TST and IGRA over time. We will utilize a community-based controlled TB household contact study design to describe both household and community M.tb exposure and infection through a standardized gradient of M.tb exposure (contact score). The standardized M. tb contact score will be a composite measure of the index case infectivity and the child's proximity and duration of contact with the TB index case. A focused set of standardized measures of age, nutrition and HIV-related immune status (CD4 T lymphocyte count) will be collected to fully assess their effect on the TST and IGRAs. Longitudinal analysis will also measure the influence of additional modifiers including time since exposure, anti-retroviral therapy, HIV viral load and isoniazid therapy. The proposed study involves primary data collection that wi-l address important gaps in our current knowledge regarding the utility and specific applicability of IGRAs for detection of M. tb infection in HIV-infected children. This includes identification of optimal cut-off values for interpretation of IGRAs in HIV-infected and -uninfected children in highly endemic settings. In HIV-infected children, those most vulnerable to TB-related morbidity and mortality IGRAs may assist in optimal clinical management through accurate and timely diagnosis and targeted preventive or curative therapy. Accurate diagnostic tools will also limit over diagnosis and treatment. Hence, IGRAs have great potential to improve TB control and decrease HIV-TB related disease and deaths in children. LAY DESCRIPTION: Novel Interferon Gamma Releases Assays have great potential to improve TB control and decrease HIV-TB related disease and deaths in children. However, it is imperative that the utility and interpretation of these tests be studied in HIV-infected children in settings with high burdens of TB and HIV.