Pathogenesis

这里概述的项目旨在确定疟疾功能性免疫的强大生物标记物，在 已注意到传播强度不同的流行地区。我们预计，使用长效杀虫剂浸泡蚊帐(LLIN)持续加强控制疟疾，并改善获得寄生虫学诊断和青蒿素联合疗法(ACT)治疗的机会，将导致免疫生物标记物水平显著降低，从而相应地丧失寄生虫学和临床免疫力。 决定疟疾感染发生率和流行率的主要控制力量 疫区疾病是指寄生虫学和临床免疫统称为自然获得性免疫(NAI)。通常，NAI不仅决定了恶性疟原虫(PF)和间日疟原虫(PV)感染的年龄别发病率和流行率，而且还决定了感染临床表现所依据的病理过程的表达。由于正在部署有效的公共卫生干预措施以减少传播，因此现在特别重要的是提高对新感染的发展和维持以及应对疟疾严重表现的能力的了解。如果采取有效的控制措施，可能会丧失非传染性疾病，从而导致在疟疾重新传入人群时易受感染的个体比例增加。这在与那些没有成功维持有效控制的国家接壤的国家尤其重要。 尽管在体外对疟疾的保护作用的绝对相关性尚不清楚，但已达成共识。 有免疫的特定生物标记物。这些包括针对裂殖子抗原(特别是侵袭配体)和/或受感染红细胞上的变异表面抗原(VSA)的血清抗体水平升高，以及强劲的淋巴细胞增殖和对血期抗原的IFNy反应。 这项研究旨在解决我们对疟疾中NAI机制的认识上的重大差距， 重点是更好地了解免疫生物标记物意味着NAI，以及细胞和体液免疫指标如何根据人群的年龄而不同地演变。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来减少疟疾传播将如何影响NAI及其持续时间。

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.