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性免疫的强大生物标志物， 已注意到不同传播强度的流行地区。我们预计，使用长效杀虫剂浸渍蚊帐（LLIN）持续强化疟疾控制以及改善寄生虫学诊断和青蒿素联合疗法（ACT）治疗的可及性将导致免疫生物标志物水平显着降低，从而导致免疫生物标志物水平显着降低。寄生虫学和临床免疫学。 决定疟疾发病率和流行率的主要控制力量 疾病流行地区的寄生虫学和临床免疫统称为自然获得性免疫（NAI）。一般来说，NAI不仅决定恶性疟原虫（Pf）和间日疟原虫（Pv）感染的年龄特异性发病率和患病率，而且还决定感染临床表现背后的病理过程的表达。由于正在部署减少传播的有效公共卫生干预措施，提高对 NAI 的发展和维持的了解以及应对疟疾严重表现的能力现在尤为重要。如果采取有效的控制措施，NAI 可能会消失，如果疟疾重新引入人群，则易感人群的比例可能会增加。这对于那些与尚未成功维持有效控制的国家接壤的国家尤其重要。 尽管体外预防疟疾的绝对相关性尚不清楚，但已达成共识 存在特定的免疫生物标志物。这些包括针对感染红细胞上裂殖子抗原（特别是入侵配体）和/或变异表面抗原（VSA）的血清抗体水平升高，以及强劲的淋巴细胞增殖和对血液阶段抗原的IFNγ反应。 这项研究有助于解决我们对疟疾 NAI 机制的认识上的重大差距， 重点是更好地了解代表 NAI 的免疫生物标志物，以及细胞和体液免疫的测量如何根据人群年龄而变化。这项研究还有助于研究疟疾传播对 NAI 的作用，以及通过普遍部署 LLIN 和 ACT 减少疟疾传播将如何影响 NAI 及其持续时间。