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

• 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
• 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

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.

职业发展目标：在HIV和疟疾神经发病机制领域从事以患者为导向的研究，成为一名独立的、富有成效的临床研究者。职业发展方法：提出了一个个性化的课程，重点培训临床研究方法，热带传染病，神经艾滋病研究和导师/教师互动。科学背景：疟疾是一种蚊子传播的寄生虫病，艾滋病毒是一种病毒感染，这是两种完全不同的致命疾病，由于地理分布的重叠，它们往往被合并在一起。尽管这些病原体经常感染同一宿主，但它们对大脑的综合影响实际上尚未得到研究。由于巨噬细胞在疟疾和艾滋病毒的发病机制中都起着重要作用，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，从而促进了艾滋病毒相关神经系统疾病（HAND）的进展。研究目的：确定疟疾合并感染对hiv相关神经认知障碍（NCI）的影响。研究方法：这项研究将在印度金奈进行，那里疟疾和艾滋病毒都非常普遍。将使用创新的汇集策略和敏感的聚合酶链反应测定法检测疟疾合并感染。通过综合神经心理学（NP）测试测量的NCI将比较艾滋病毒/疟疾合并感染和艾滋病毒单一感染参与者之间的NCI。除了测量病原体活性外，还将测量血液中的炎症相关生物标志物（IAB）。NP表现的变化将与疟疾治疗前后艾滋病毒/疟疾共感染组中病原体活性和炎症指标的变化进行比较。综合起来，这些结果将首次确定疟疾对与艾滋病毒相关的非传染性疾病的贡献以及治疗疟疾的影响。意义：这些研究将导致- i)通过检测和治疗疟疾合并感染来改善艾滋病毒/艾滋病护理；ii)证明艾滋病毒/疟疾合并感染对大脑的不利影响；Iii)促进该领域的进一步研究。未确诊的疟疾合并感染的负面影响可能证明，在世界疟疾流行地区的艾滋病毒感染者的常规临床护理中，与聚合酶链反应相关的费用是合理的。从这项研究中获得的知识将显著改善成人艾滋病毒和疟疾相关神经行为缺陷的评估、诊断和治疗。