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

干扰素-γ释放测定在结核病-艾滋病毒合并感染儿童中的应用

• 批准号: 7470105
• 负责人: ANNA M MANDALAKAS
• 金额: $ 54.43万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470105
• 关键词: Address; Adult; Africa South of the Sahara; Age; Age-Years; Agreement; Anti-Retroviral Agents; Antigens; Antitubercular Agents; Asses; Biological Assay; CD4 Positive T Lymphocytes; Calmette-Guerin Bacillus; Caring; Cause of Death; Cell Count; Cessation of life; Child; Child health care; Childhood; Clinical Management; Communities; Confounding Factors (Epidemiology); Contracts; Data; Data Collection; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Effectiveness; Enrollment; Exposure to; Genus Mycobacterium; Gold; HIV-1; Health Benefit; Household; Hypersensitivity skin testing; Immune; Immunization; Immunologic Markers; Infection; Institution; Interferon Type II; Knowledge; Lymphocyte Count; Measures; Methods; Morbidity - disease rate; Mycobacterium tuberculosis; Nutritional; Nutritional status; Performance; Population; Prevention; Preventive; Production; Public Health; Reporting; Research Design; Research Personnel; Risk; Score; Specificity; Standards of Weights and Measures; T-Lymphocyte; Testing; Time; Tube; Tuberculin; Tuberculosis; Vaccination; Viral Load result; aging nutrition; base; design; diagnostic accuracy; improved; indexing; interest; isoniazid; mortality; novel; prospective; response; tool

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.

描述(申请人提供)：我们项目的主要目标是通过准确识别感染结核分枝杆菌的儿童，改善感染人类免疫缺陷病毒-1(HIV)和结核分枝杆菌(M.TB)混合感染的儿童的健康。这项研究旨在检查干扰素-伽玛释放试验(IGRA)在结核分枝杆菌和艾滋病毒混合感染儿童中的实用性和解释。关于使用IGRA检测艾滋病毒感染儿童中结核分枝杆菌感染的数据有限/在结核病(TB)和艾滋病毒高度流行的背景下进行的一项基于社区的前瞻性研究中，将在5岁以下的艾滋病毒感染儿童(N=300)和未感染儿童(N=500)中解决以下具体目标：1)评估传统的结核菌素皮肤试验(TST)和IGRA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)测量潜在交互作用和混杂变量的影响；4)找出随时间推移影响儿童对TST和IGRA反应的因素。我们将利用以社区为基础的受控结核病家庭接触研究设计来描述家庭和社区结核分枝杆菌的暴露和通过结核分枝杆菌暴露的标准化梯度(接触得分)进行的感染。标准化的结核分枝杆菌接触评分将是对指示病例传染性以及儿童与结核病指示病例的接触程度和持续时间的综合衡量。将收集一套针对年龄、营养和艾滋病毒相关免疫状态(CD4T淋巴细胞计数)的标准化衡量标准，以全面评估它们对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。这项拟议的研究涉及初步数据收集，以解决我们目前关于IGRAs在检测HIV感染儿童中结核分枝杆菌感染的实用性和特殊适用性方面的重要知识空白。这包括在高度流行的环境中确定解释艾滋病毒感染儿童和未感染儿童免疫球蛋白受体的最佳分界值。在感染艾滋病毒的儿童中，最容易受到结核病相关发病率和死亡率影响的IGRAs可以通过准确和及时的诊断和有针对性的预防或治疗来帮助进行最佳的临床管理。准确的诊断工具也将限制过度的诊断和治疗。因此，IGRA在改善结核病控制和减少儿童中艾滋病毒-结核病相关疾病和死亡方面具有巨大潜力。行业描述：新的干扰素伽玛释放试验具有改善结核病控制和减少儿童中艾滋病毒-结核病相关疾病和死亡的巨大潜力。然而，当务之急是在结核病和艾滋病毒高负担的环境中研究这些检测在艾滋病毒感染儿童中的实用性和解释。