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通过准确识别结核分枝杆菌感染者，改善人类免疫缺陷病毒-1 （HIV）和结核分枝杆菌（M. tb）合并感染儿童的健康状况。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合并感染儿童中的效用和解释。关于使用IGRA检测艾滋病毒感染儿童结核分枝杆菌感染的数据有限/在结核病和艾滋病毒高度流行的环境中进行的前瞻性社区研究中，将在艾滋病毒感染（N=300）和未感染（N=500）的5岁以下儿童中实现以下具体目标：1)评估传统结核菌素皮肤试验（TST）和IGRAs之间的一致性，2)评估TST和IGRAs在结核分枝杆菌暴露标准梯度上的表现，3)测量潜在相互作用和混杂变量的影响，以及4)确定随时间推移改变儿童对TST和IGRA反应的因素。我们将利用社区控制结核家庭接触研究设计，通过结核接触的标准化梯度（接触评分）描述家庭和社区结核接触和感染情况。标准化结核分枝杆菌接触评分将是指标病例传染性以及儿童与结核病指标病例接触的距离和持续时间的综合衡量标准。将收集年龄、营养和艾滋病毒相关免疫状态（CD4 T淋巴细胞计数）的一套重点标准化措施，以充分评估它们对TST和IGRAs的影响。纵向分析还将衡量其他修饰因素的影响，包括暴露时间、抗逆转录病毒治疗、艾滋病毒载量和异烟肼治疗。拟议的研究涉及原始数据收集，wi- 1解决了我们目前关于IGRAs用于检测艾滋病毒感染儿童结核分枝杆菌感染的效用和特定适用性的知识的重要空白。这包括在高度流行的环境中确定解释艾滋病毒感染和未感染儿童IGRAs的最佳临界值。在感染艾滋病毒的儿童中，那些最容易受到结核病相关发病率和死亡率影响的儿童可通过准确和及时的诊断以及有针对性的预防或治疗治疗，协助进行最佳临床管理。准确的诊断工具也将限制过度诊断和治疗。因此，IGRAs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。描述：新型干扰素γ释放测定法在改善结核病控制和减少儿童HIV-TB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对这些检测的效用和解释进行研究。

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.