Impact of Malaria Co-Infection on HIV-Associated Neurocognitive Disorders

疟疾合并感染对 HIV 相关神经认知障碍的影响

基本信息

批准号：
8526559
负责人：
AJAY R BHARTI
金额：
$ 17.05万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-15 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8526559
关键词：
AIDS neuropathy AIDS/HIV problem Abbreviations Accounting Acquired Immunodeficiency Syndrome Activities of Daily Living Address Adult Adverse effects Age Apoptosis Beck depression inventory Behavioral Biological Assay Biological Markers Blood Brain Brain Injuries CCL2 gene CD14 gene CD4 Lymphocyte Count CD40 Ligand Caring Cell Adhesion Molecules Centers for Disease Control and Prevention (U.S.)Cerebrum Characteristics Cities Clinical Clinical Investigator Clinical Research Cognitive Communicable Diseases Cost Savings Culicidae Cytokine Network Pathway Data Data Analyses Detection Diagnosis Disease Disease Progression Education Educational Curriculum Elements Employment Epidemiology Ethnic Origin Faculty Frequencies Future Geographic Distribution Glossary HIV HIV-1 Hemoglobin Hour Impairment India Individual Individual Differences Infection Inflammation Inflammation Mediators Injury Insulin-Like Growth Factor I Integration Host Factors Intercellular adhesion molecule 1 Interferons Interleukin-1 Interleukin-6 Investigation Knowledge Lead Link Location Macrophage Activation Malaria Malnutrition Measurement Measures Mediating Mentors Methods Microscopy Moods Neopterin Nervous system structure Neurocognitive Neurologic Neuropathogenesis Neuroprotective Agents Neuropsychological Tests Neurotoxins Observational Study Outcome Oxidative Stress Parasitemia Parasitic Diseases Participant Pathogenesis Performance Plasma Polymerase Chain Reaction Production RNA Research Research Methodology Research Personnel Role Serum Serum Albumin Severities Sleep Sleep Deprivation Specimen Staging T-Cell Activation TNF gene Testing Time Training Treatment outcome Urokinase Plasminogen Activator Receptor Virus Diseases Vivax Malaria acronyms base career career development clinical care cost cytokine design hemozoin improved innovation isoprostaglandin F2alpha type-III macrophage mild neurocognitive impairment nervous system disorder neurobehavioral neuropsychological pathogen patient oriented research public health relevance transmission process

AIDS neuropathy AIDS/HIV problem Abbreviations Accounting Acquired Immunodeficiency Syndrome Activities of Daily Living Address Adult Adverse effects Age Apoptosis Beck depression inventory Behavioral Biological Assay Biological Markers Blood Brain Brain Injuries CCL2 gene CD14 gene CD4 Lymphocyte Count CD40 Ligand Caring Cell Adhesion Molecules Centers for Disease Control and Prevention (U.S.)Cerebrum Characteristics Cities Clinical Clinical Investigator Clinical Research Cognitive Communicable Diseases Cost Savings Culicidae Cytokine Network Pathway Data Data Analyses Detection Diagnosis Disease Disease Progression Education Educational Curriculum Elements Employment Epidemiology Ethnic Origin Faculty Frequencies Future Geographic Distribution Glossary HIV HIV-1 Hemoglobin Hour Impairment India Individual Individual Differences Infection Inflammation Inflammation Mediators Injury Insulin-Like Growth Factor I Integration Host Factors Intercellular adhesion molecule 1 Interferons Interleukin-1 Interleukin-6 Investigation Knowledge Lead Link Location Macrophage Activation Malaria Malnutrition Measurement Measures Mediating Mentors Methods Microscopy Moods Neopterin Nervous system structure Neurocognitive Neurologic Neuropathogenesis Neuroprotective Agents Neuropsychological Tests Neurotoxins Observational Study Outcome Oxidative Stress Parasitemia Parasitic Diseases Participant Pathogenesis Performance Plasma Polymerase Chain Reaction Production RNA Research Research Methodology Research Personnel Role Serum Serum Albumin Severities Sleep Sleep Deprivation Specimen Staging T-Cell Activation TNF gene Testing Time Training Treatment outcome Urokinase Plasminogen Activator Receptor Virus Diseases Vivax Malaria acronyms base career career development clinical care cost cytokine design hemozoin improved innovation isoprostaglandin F2alpha type-III macrophage mild neurocognitive impairment nervous system disorder neurobehavioral neuropsychological pathogen patient oriented research public health relevance transmission process

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项目摘要

DESCRIPTION (provided by applicant): Career Development Aim: To develop into an independent, productive clinical investigator focusing on patient-oriented research in the field of HIV and malaria neuropathogenesis. Career Development Methods: An individualized curriculum with focused training in clinical research methodology, tropical infectious diseases, NeuroAIDS research, and mentor/faculty interactions is proposed. Scientific Background: Malaria, a mosquito-borne parasitic disease, and HIV, a viral infection, are two disparate and deadly diseases that are often brought together by overlapping geographic distributions. Even though these pathogens frequently infect the same host, their combined effects on the brain are virtually uninvestigated. Since macrophages are centrally involved in both malaria and HIV pathogenesis, we hypothesize that both of these pathogens disrupt the cytokine network of brain macrophages, thereby contributing to the progression of HIV-associated neurologic disorders (HAND). Research Aim: To determine the impact of malaria co-infection on HIV-associated neurocognitive impairment (NCI). Research Methods: This study will be conducted in Chennai, India where both malaria and HIV are highly prevalent. Malaria co-infection will be detected using an innovative pooling strategy and a sensitive Polymerase Chain Reaction assay. NCI, measured by comprehensive neuropsychological (NP) testing, will be compared between HIV/malaria co-infected and HIV-monoinfected participants. In addition to measures of pathogen activity, a panel of inflammation-associated biomarkers (IAB) will be measured in blood. Changes in NP performance will be compared to changes in measures of pathogen activity and inflammation in the HIV/malaria co-infected group before and after malaria therapy. Combined, these results will identify, for the first time, the contribution of malaria to HIV-associated NCI and the impact of treating malaria. Significance: These studies will lead to - i) improvement in HIV/AIDS care through detection and treatment of malaria coinfection; ii) demonstrate the adverse effect of HIV/malaria co-infection on the brain; iii) stimulate further research in this field. The negative impact of undiagnosed malaria co-infection may justify PCR-related expenses in routine clinical care of HIV-infected individuals in malaria endemic regions of the world. The knowledge gained from this study will significantly improve the assessment, diagnosis, and hence treatment of HIV and malaria associated neurobehavioral deficits among adults.

描述（由申请人提供）：职业发展目的：发展成为一个独立的，生产性的临床研究者，专注于艾滋病毒和疟疾神经病生成领域的以患者为导向的研究。职业发展方法：提出了一种个性化的课程，并提出了临床研究方法，热带传染病，神经辅助研究和导师/教师互动的重点培训。科学背景：疟疾，一种蚊子传播的寄生虫病，艾滋病毒是一种病毒感染，是两种不同的和致命的疾病，通常通过重叠的地理分布将其汇集在一起。即使这些病原体经常感染相同的宿主，它们对大脑的综合作用实际上也没有进行研究。由于巨噬细胞集中参与疟疾和HIV发病机理，因此我们假设这两种病原体都破坏了脑巨噬细胞的细胞因子网络，从而有助于与HIV相关的神经系统疾病的进展（手）。研究目的：确定疟疾共感染对与HIV相关的神经认知障碍（NCI）的影响。研究方法：这项研究将在印度钦奈进行，那里的疟疾和艾滋病毒都非常普遍。疟疾共感染将使用创新的合并策略和灵敏的聚合酶链反应测定法检测。通过全面的神经心理学（NP）测试来衡量的NCI将在HIV/疟疾共感染和HIV - 单位感染的参与者之间进行比较。除了病原活性的测量外，还将在血液中测量一组炎症相关的生物标志物（IAB）。 NP性能的变化将与疟疾治疗前后HIV/疟疾共感染组的病原体活性和炎症的度量的变化进行比较。这些结果结合在一起，将首次确定疟疾对与HIV相关的NCI的贡献以及治疗疟疾的影响。意义：这些研究将导致-i）通过发现和治疗疟疾共感染来改善HIV/艾滋病护理； ii）证明HIV/疟疾共感染对大脑的不利影响； iii）刺激该领域的进一步研究。未经诊断的疟疾共感染的负面影响可能证明世界上疟疾中流行地区的HIV感染者常规临床护理中与PCR相关的费用是合理的。从这项研究中获得的知识将显着改善成人艾滋病毒和疟疾相关的艾滋病毒和疟疾的评估，并因此治疗。