Epidemiology and transmission of subclinical malaria

缅甸区域ICEMR项目1解决了研究领域A（流行病学）和B（ 传输消灭疟疾可能需要根除所有感染者身上的所有寄生虫，而不仅仅是那些 临床症状。如果临床疟疾代表了“冰山一角”，那么了解其余的 冰山-它是否对受感染者构成风险甚至有益，以及它如何有助于传播， 不同的流行病学环境对控制和消灭疟疾很重要。使用超灵敏的 逆转录聚合酶链反应（usPCR）检测，我们发现高度异质性疟疾流行的疟疾 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）。 根据亚临床疟疾流行率， usPCR。然而，以前的研究没有评估临床风险或传播潜力的， 通过这些测试检测出极低密度的疟疾感染。项目1的第一个目标是衡量 亚临床疟疾感染的动态，并评估其对临床疟疾风险的影响， 在东南亚的传播潜力。我们假设持续的亚临床恶性疟原虫 和间日疟原虫感染代表慢性感染，可预防疟疾的临床表现， 亚临床疟疾感染是一个潜在的传播源。多中心、匹配队列 研究将在缅甸及其与中国和孟加拉国沿着的六个地点进行。usPCR将 用于测量亚临床超低密度恶性疟原虫和间日疟原虫的流行率和动态 感染亚临床感染与临床疟疾发病率和传染性之间的关系将在 使用多变量和事件发生时间模型估计。这一目标将产生证据来指导 关于MDA和其他消除干预措施的建议。我们还设计并使用蛋白质， 肽微阵列，用于测量对多种疟疾的大量变体的抗体反应， 蚊子蛋白这些微阵列可能被证明是有用的监测工具，以衡量接触寄生虫 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， 基因型第二个目标是估计最近和遥远的接触疟疾寄生虫和病媒， 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， 假设对恶性疟原虫和间日疟原虫抗原的不同变体的抗体应答是相关的 与暴露于新的疟疾感染;抗体反应，以不同的按蚊抗原是独立的 与蚊虫接触的风险因素以及当地病媒的多样性和数量有关;以及 对配子体蛋白的血清反应性与感染性有关。这一目标将产生一套信息丰富的 蛋白质和/或肽可用于监测工具，以指导消除干预，具有进一步研究的潜力。 发展成为一种即时血清监测检测，以帮助消除疟疾项目对疟疾风险进行分层。

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.