Epidemiology of Malaria in Malawi: Human Hosts and Parasites in Three Districts

尽管在过去的30年里，我们对疟疾生物学的理解有了显著的进步， 在撒哈拉以南非洲的大部分地区，消灭甚至控制疟疾仍然遥遥无期。在这项提案中，我们将确定马拉维疟疾疾病和感染的负担，并为控制和消除疟疾的努力提供最先进的科学方法，以应用新的干预措施，以既定的干预措施为目标，并迅速准确地评估其影响。马拉维是一个受疟疾严重打击的国家，它在决策者和投资者之间有着良好的合作关系，并拥有支持本申请中提出的新方法的物质和科学基础设施。 项目1的总体目标是描述疟疾流行病学的变化， 在马拉维不同的流行病学背景下，控制和消除疟疾的努力，并了解这种不断变化的流行病学如何影响疟疾疾病的负担，疟疾感染的水库，以及抗疟药物耐药性的出现和传播（或逆转）。这些目标将通过以下三个具体目标实现：1）评估马拉维不同生态地理区域疟疾感染和疾病的负担，以及与控制和消除干预措施的关系，2）描述马拉维不同生态地理区域的寄生虫种群遗传学特征，并对疟疾控制和消除干预措施作出反应，3）衡量抗疟药物政策变化对耐药寄生虫流行的影响。这些目标将通过在布兰太尔、蒂约洛和奇夸瓦地区进行横断面研究、基于保健设施的监测和小规模但详细的队列研究来实现，以准确界定疾病和感染负担，并查明传播源。将对从这些来源收集的标本进行基因组分析，以评估传播强度对人口基因组的影响，为马拉维开发适合实地的基因工具，并检测由于新药物的使用而导致的耐药性模式的变化。 施政纲要而

Despite remarkable advances in our understanding of the biology of malaria in the last 30 years, malaria eliminafion, or even control, remains on the distant horizon in most of sub-Saharan Africa. In this proposal, we will define the burden of malaria disease and infecfion in Malawi and bring to control and elimination efforts the most advanced scientific methods available to apply new interventions, target established ones and assess their impact rapidly and accurately. Malawi is a country hit hard by malaria, it has an excellent collaborative relafionship between policy-makers and invesfigators and the physical and scientific infrastructure to support the novel approaches proposed in this application. The overall goal of Project 1 is to characterize the changing epidemiology of malaria in response to control and eliminafion efforts in diverse epidemiological setfings within Malawi, and to understand how this changing epidemiology affects the burden of malaria disease, the reservoir of malaria infection, and the emergence and spread (or reversal) of resistance to anfimalarial drugs. These goals will be accomplished through the following three specific aims: 1) to evaluate the burden of malaria infecfion and disease in diverse eco-geographic regions of Malawi and in relafion to control and eliminafion intervenfions, 2) to characterize the parasite population genetics in diverse eco-geographic regions of Malawi and in response to malaria control and elimination interventions and 3) to measure the effect of changes in antimalarial drug policy on the prevalence of drug-resistant parasites. These aims will be accomplished through crosssectional studies, health facility-based surveillance and small but detailed cohort studies in Blantyre, Thyolo and Chikwawa districts to accurately define the burden of disease and infection and detect sources of transmission. Specimens collected from these sources will undergo genomic analysis for the purposes of assessing the effect of transmission intensity on population genefics, the development of field-appropriate genetic tools for Malawi and for detecting changes in drug-resistance patterns as a result of new drug policies.