Pathogenesis

发病

• 批准号: 8293255
• 负责人: Christopher L King
• 金额: $ 16.11万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8293255
• 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的功能性免疫的强有力的生物标志物， 已注意到不同传播强度的流行地区。我们预计，使用长效驱虫蚊帐（LLINs）持续、强化控制疟疾，以及改善利用青蒿素联合疗法（ACT）进行寄生虫学诊断和治疗的机会，将导致免疫生物标志物水平显著降低，从而相应地丧失寄生虫学和临床免疫力。 是决定疟疾发病率和流行率的主要控制力量， 在流行地区的疾病是寄生虫学和临床免疫统称为自然获得性免疫（NAI）。一般而言，NAI不仅决定了恶性疟原虫（Pf）和间日疟原虫（Pv）感染的年龄特异性发病率和患病率，而且还决定了感染临床表现的病理过程的表达。提高对NAI的发展和维持的理解以及科普疟疾严重表现的能力现在尤其重要，因为正在部署减少传播的有效公共卫生干预措施。如果采取有效的控制措施，NAI可能会丧失，从而导致如果疟疾重新引入人群，个体变得易感的比例增加。这一点在与未能成功维持有效控制的国家接壤的国家尤其重要。 虽然在体外与疟疾的保护作用的绝对相关性尚不清楚，但已达成共识 免疫力有特定的生物标志物。这些包括针对感染红细胞上的裂殖子抗原（特别是侵袭配体）和/或变体表面抗原（VSA）的血清抗体水平升高，以及对血液阶段抗原的强烈淋巴细胞增殖和IFN γ应答。 这项研究有助于解决我们在疟疾NAI机制知识方面的重大差距， 重点是更好地了解什么免疫生物标志物意味着NAI，以及细胞和体液免疫的措施如何根据人群的年龄差异发展。本研究还探讨了疟疾传播对NAI的作用，以及通过普遍部署长效驱虫蚊帐和青蒿素综合疗法减少疟疾传播对NAI及其持续时间的影响。