Epidemiology and transmission of subclinical malaria

缅甸区域ICEMR项目1涉及研究领域A、流行病学和B中的问题， 变速箱。消除疟疾可能需要根除所有感染者的所有寄生虫，而不仅仅是那些 有临床症状。如果临床疟疾只是冰山一角，那么理解 冰山-它是否对感染者构成风险或甚至是好处，以及它如何促进在 不同的流行病学环境对控制和消除疟疾将是重要的。使用超灵敏的 逆转录聚合酶链式反应(UsPCR)分析，我们发现疟疾流行具有高度的异质性 在缅甸。世界卫生组织最近批准了东南部的大规模药物管理(MDA) 亚洲，目前正在缅甸开展基于以下测量的亚临床疟疾流行率的MDA UsPCR.然而，以前没有研究评估过这种病毒的临床风险或传播潜力。 通过这些检测检测到极低密度的疟疾感染。项目1的第一个目标是测量 亚临床疟疾感染的动态，并评估其对临床疟疾风险的贡献 东南亚的传播潜力。我们假设持续性亚临床恶性疟原虫 和间日疟原虫感染是一种慢性感染，可预防疟疾的临床表现，以及 亚临床疟疾感染是潜在的传播源。多中心、匹配的队列 研究将在缅甸以及与中国和孟加拉国接壤的边境沿线的六个地点进行。UsPCR将 用来测量亚临床超低密度恶性疟原虫和间日疟原虫的流行和动态 感染。亚临床感染与临床疟疾发病率和传染性的关系将是 使用多变量和事件发生时间模型进行估计。这一目标将产生证据来指导 关于丙二醛和其他消除干预措施的建议。我们还设计并使用了蛋白质和 多肽微阵列用于测量对多种疟疾和 蚊子蛋白质。这些微阵列可能会被证明是有用的监测工具，以测量寄生虫的暴露 和蚊子，并提供了一种方法来表征低密度感染的遗传多样性，这些感染很难 基因分型。第二个目标是估计最近和远程接触疟疾寄生虫和媒介的情况。 人类使用这些阵列来测量对不同疟疾和蚊子抗原的血清反应性，测试 假设对恶性疟原虫和间日疟原虫不同变种的抗体反应是相关的 暴露于新的疟疾感染；对不同按蚊抗原的抗体反应是独立的 与蚊子暴露的风险因素以及当地媒介的多样性和丰富性有关；以及 配子体蛋白的血清反应性与传染性有关。这一目标将产生一组信息性的 可用于指导消除干预措施的监测工具的蛋白质和/或肽，有可能进一步 开发作为一种医疗保健点血清监测测试，以帮助消除疟疾计划分层疟疾风险。

Project 1 of the Myanmar Regional ICEMR addresses questions in Research Areas A, Epidemiology and B, Transmission. Malaria elimination may require eradicating all parasites from all infected persons, not just those with clinical symptoms. If clinical malaria represents the “tip of the iceberg”, understanding the rest of the iceberg—whether it poses risk or even benefit to infected individuals, and how it contributes to transmission in different epidemiological settings—will be important for malaria control and elimination. Using an ultrasensitive reverse transcription PCR (usPCR) assay, we are finding highly heterogeneous malaria prevalence of malaria in Myanmar. The World Health Organization recently endorsed mass drug administration (MDA) in Southeast Asia, and MDA is being undertaken in Myanmar based on subclinical malaria prevalence as measured by usPCR. However, no previous studies have assessed the clinical risks or transmission potential of the extremely low density malaria infections detected by these tests. The first aim of Project 1 is to measure the dynamics of subclinical malaria infections and assess their contribution to the risk of clinical malaria and to transmission potential in Southeast Asia. We hypothesize that persistent subclinical Plasmodium falciparum and P. vivax infections represent chronic infection that protects against clinical manifestations of malaria, and that subclinical malaria infections represent a potential source of transmission. A multicenter, matched cohort study will be conducted at six sites in Myanmar and along its borders with China and Bangladesh. usPCR will be used to measure the prevalence and dynamics of subclinical ultralow density P. falciparum and P. vivax infection. The association of subclinical infection with incidence of clinical malaria and infectivity will be estimated using multivariate and time-to-event models. This aim will generate evidence to guide recommendations about MDA and other elimination interventions. We also designed and are using protein and peptide microarrays to measure antibody responses to large numbers of variants of diverse malaria and mosquito proteins. These microarrays may prove useful as surveillance tools to measure exposure to parasites and mosquitoes, and provide a way to characterize genetic diversity in low density infections that are difficult to genotype. The second aim is to estimate recent and remote exposure to malaria parasites and vectors in humans using these arrays to measure seroreactivity to diverse malaria and mosquito antigens, testing the hypotheses that antibody responses to diverse variants of P. falciparum and P. vivax antigens are associated with exposure to new malaria infections; antibody responses to diverse Anopheles antigens are independently associated with risk factors for mosquito exposure and with local vector diversity and abundance; and seroreactivity to gametocyte proteins is associated with infectivity. This aim will generate sets of informative proteins and/or peptides useful for surveillance tools to guide elimination interventions, with potential for further development as a point-of-care sero-surveillance test to help malaria elimination programs stratify malaria risk.