Pathogenesis

发病

• 批准号: 8494538
• 负责人: Christopher L King
• 金额: $ 17.67万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494538
• 关键词: Acidosis; Address; Adult; Affect; Age; Anemia; Antibodies; Antigens; Area; Artemisinins; Asia; B-Lymphocytes; Beds; Biological Assay; Biological Markers; Blood; Cellular Immunity; Characteristics; Child; Clinical; Cohort Studies; Combined Modality Therapy; Communities; Consensus; Country; Development; Diagnosis; Disease; Epidemiology; Erythrocytes; Evaluation; Exposure to; Fever; Frequencies; Funding; Growth; Hemoglobin; High Prevalence; Homologous Gene; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunobiology; Immunologic Markers; Improve Access; In Vitro; Incidence; Individual; Infection; Insecticides; Intervention; Knowledge; Life; Ligands; Liver; Longevity; Madagascar; Maintenance; Malaise; Malaria; Malaria Vaccines; Measures; Mediating; Memory; Neurologic; Parasitemia; Parasites; Pathogenesis; Pathologic Processes; Phenotype; Plasmodium falciparum; Population; Prevalence; Proteins; Public Health; Relapse; Relative (related person); Research; Research Project Grants; Resistance; Risk; Role; Serum; Site; Staging; Surface Antigens; Syphilis; T memory cell; T-Lymphocyte; Testing; Time; Vaccines; Variant; acquired immunity; age effect; artemisinine; coping; design; improved; lymphocyte proliferation; novel; parasite invasion; pathogen; prevent; programs; response; tool; transmission process

The project outlined here seeks to identify robust biomarkers of functional immunity to malaria, In endemic areas where differing transmission intensities have been noted. We anticipate that sustained, intensified control of malaria using long-lasting Insecticide Impregnated bed nets (LLINs) and Improved access to parasitological diagnosis and treatment with artemisinin combination therapy (ACT) will result In significantly lower levels of immune biomarkers, thus corresponding to a loss of parasitological and clinical Immunity. A major controlling force that determines the incidence and prevalence of malaria Infection and disease in endemic areas is the parasitological and clinical Immunity collectively refen'ed to as naturally acquired Immunity (NAI). Generally, NAI determines not only the age-speciflc Incidence and prevalence of P. falciparum (Pf) and P. vivax (Pv) infection, but also the expression of pathological processes that underlie the clinical manifestations of Infection. Improved understanding ofthe development and maintenance of NAI and the ability to cope with the severe manifestations of malaria are now particulariy Important, since effective public health interventions that reduce transmission are being deployed. With effective control measures NAI may be lost, resulting in an increased proportion of Individuals becoming susceptible should malaria be re-introduced to the population. This is especially Important in countries that border those where effective control has not been successfully maintained. Although absolute in vitro correlates of protection to malaria are unknown, consensus has emerged that there are specific biomarkers of immunity. These include elevated levels of serum antibodies directed at merozoite antigens (particulariy Invasion ligands) and/or variant surface antigen (VSA) on Infected erythrocytes, as well as robust lymphocyte proliferation and IFNy responses to blood-stage antigens. This study alms to address significant gaps in our knowledge of NAI mechanisms In malaria, with a focus to better understand what immune biomarkers signify NAI, and how measures of cellular and humoral Immunity evolve differentially according to age in populations. This study also alms to examine of the role of malaria transmission on NAI, and how reduction of malaria transmission by universal deployment of LLINs and ACT will affect NAI and Its duration.

这里概述的项目旨在确定对疟疾功能免疫的强大生物标志物， 已经注意到传播强度不同的地方性地区。我们预计，使用长期杀虫剂浸渍床网（LLIN）对疟疾的持续，加强控制，并改善了对寄生虫学诊断和通过青蒿素联合治疗（ACT）进行治疗的机会，将导致免疫生物标志物的水平明显降低，从而与寄生虫学和政府学免疫失去相对应。 决定疟疾感染的发病率和患病率的主要控制力 流行地区的疾病是寄生虫和临床免疫，共同恢复为自然获得的免疫力（NAI）。通常，NAI不仅确定了恶性疟原虫（PF）和V. Vivax（PV）感染的年龄特异性发生率和患病率，还决定了感染临床表现的病理过程的表达。现在，人们对NAI的发展和维护的了解以及应对疟疾严重表现的能力的了解至关重要，因为部署了减少传播的有效公共卫生干预措施。使用有效的控制措施，NAI可能会丢失，如果将疟疾重新引入人群，则会增加易感性的个体。这在与未能成功维护的有效控制的国家相提并论的国家尤其重要。 尽管绝对在体外保护与疟疾的保护相关性尚不清楚，但已经出现了共识 有特定的免疫生物标志物。其中包括针对梅罗唑帝国抗原（特定的浸润配体）和/或变体表面抗原（VSA）的血清抗体水平升高，以及对感染性红细胞的变异表面抗原（VSA），以及对血液阶段抗原的强大淋巴细胞增殖和IFNY反应。 这项研究施加了解决我们对疟疾NAI机制知识的显着差距， 专注于更好地了解哪种免疫生物标志物表示NAI的含义，以及根据人群年龄的年龄，细胞和体液免疫的测量如何差异化。这项研究还施加了检查疟疾在NAI上的作用，以及通过普遍部署LLIN和ACT的疟疾传播如何影响NAI及其持续时间。