Understanding, tracking and eliminating malaria transmission in the Asia - Pacific Region

了解、追踪和消除亚太地区的疟疾传播

• 批准号: 10609039
• 负责人: Ivo J Mueller
• 金额: $ 62.8万
• 依托单位: WALTER AND ELIZA HALL INST MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-28 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10609039
• 关键词: 4-aminoquinoline; Address; Affect; Anopheles Genus; Antibodies; Antimalarials; Area; Artemisinins; Asia; Biological; Biological Assay; Biology; Biometry; Bite; Cambodia; Chronic; Clinical; Cohort Studies; Computer Simulation; Country; Cross-Sectional Studies; Culicidae; Data; Detection; Development; Disease; Drops; Drug resistance; Effectiveness; Epidemiology; Exposure to; Far East; Genomics; Genotype; Goals; Health care facility; Human; Immune response; Immunologics; Immunology; Individual; Infection; Integration Host Factors; Knowledge; Link; Liver; Longitudinal Studies; Longitudinal cohort study; Malaria; Membrane; Methods; Modeling; Molecular; Molecular Diagnosis; Movement; New Guinea; Parasite resistance; Parasites; Pattern; Persons; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Play; Politics; Population; Population Group; Predisposition; Primary Infection; Relapse; Research Design; Residual state; Resistance; Resistance development; Resources; Risk; Risk Factors; Role; Salivary Proteins; Sampling; Series; Site; Systems Biology; Testing; Thailand; Variant; clinical effect; cohort; cost; design; epidemiologic data; epidemiology study; feeding; fitness; high risk; high risk population; high throughput screening; improved; in silico; infection risk; innovation; malaria infection; malaria transmission; mathematical model; molecular marker; multidisciplinary; next generation sequencing; novel strategies; programs; promote resilience; public health emergency; resilience; resistant Plasmodium falciparum; spatiotemporal; surveillance strategy; symposium; tool; transmission process; vector; vector mosquito

Summary As the Asia-Pacific aim to eliminate malaria from the entire region by 2030, a number of key challenges related to increasing strong variations in malaria transmission, the presence of a large reservoir of infected but asymptomatic individual and the development of resistance to frontline antimalarial treatment need to be confronted. In addition, the predominance of P. vivax infections in the region results in the particular challenge of dealing with P. vivax hypnozoites and the relapsing infections the cause. The Asia-Pacific ICEMR project is proposing to conduct coordinated set of field and in-depth biological studies in 3 sites in Cambodia, Papua New Guinea and Thailand that span the range of transmission intensities currently found in the Asia-Pacific regions. In the Epidemiology Project spatio-temporal patterns of risk of malaria infection and disease will be investigate through a combination of large cross-sectional and longitudinal cohort studies that combine excellent epidemiological study designs with state-of-the-art molecular detection and genotyping of Plasmodium spp. infections and an assessment of host immune responses and their link to exposure and clinical protection. The information thus gained will be used to evaluate improved surveillance strategies through an innovative combination of computer simulations and field application. The Transmission Project will use direct membrane feeding assay as a xenodiagnostic tool to determine the infective reservoir as each site and investigate host, parasite and host factors that contribute to sustaining endemic transmission at each site. In addition, we will study patterns of human-vector contact in low transmission settings by investigating human antibodies to anopheline salivary protein as marker exposure to mosquito bites. A key question in both studies is how artemisinin and partner drug resistance affects parasite fitness both in chronic asymptomatic infections and transmissibility. Finally, the P. vivax Relapse Project will specifically address the role of relapsing infections from long-lasting liver stages in the increased resilience of P. vivax against control and elimination. The conduct of these studies will use spatially explicit malaria transmission models, next- generation sequencing (NGS)-based high-throughput genotyping methods and a range of high-throughput and functional assay of humoral immune responses that will be developed in 3 resource cores. These interconnected, multi-disciplinary studies thus aim to identify and characterize critical steps in malaria transmission cycle and thereby gain a better understanding of parasite, host and vector factors that contribute to continued transmission in the context of intensive national malaria control and elimination programs. This knowledge will assist in the development of novel approaches to target residual transmission pockets.

总结 随着亚太区域的目标是到2030年在整个区域消除疟疾， 由于疟疾传播的变化越来越大， 无症状个体和对一线抗疟治疗产生耐药性需要 对峙此外，该地区间日疟原虫感染的优势导致了特别的挑战， 间日疟原虫催眠虫和复发性感染的原因。亚太ICEMR项目是 建议在柬埔寨、巴布亚和柬埔寨的3个地点进行一系列协调一致的实地和深入生物研究 新几内亚和泰国，跨越目前在亚太地区发现的传播强度范围 地区在流行病学项目中，将研究疟疾感染和疾病风险的时空模式， 通过大规模横断面和纵向队列研究相结合，研究联合收割机 优秀的流行病学研究设计，具有最先进的分子检测和基因分型， 疟原虫属感染和评估宿主免疫反应及其与接触的联系， 临床保护由此获得的信息将用于评估改进的监测战略 通过计算机模拟和现场应用的创新组合。传输项目 将使用直接膜饲养试验作为异种诊断工具，以确定感染性储库， 确定并调查在每一个地点有助于维持地方病传播的宿主、寄生虫和宿主因素 绝佳的价钱此外，我们还将通过调查研究低传播环境中人与病媒接触的模式， 人按蚊唾液蛋白抗体作为暴露于蚊虫叮咬的标志。两者的关键问题是 研究表明，青蒿素及其伙伴的耐药性如何影响慢性无症状和慢性无症状感染者的寄生虫适应度。 感染和传染性。最后，间日疟原虫复发项目将专门讨论以下因素的作用： 在间日疟原虫对控制的恢复力增加中，来自长期肝脏阶段的复发性感染， 淘汰开展这些研究将使用空间上明确的疟疾传播模型，接下来- 代测序（NGS）为基础的高通量基因分型方法和一系列的高通量和 将在3个资源核心中开发的体液免疫应答的功能测定。这些 因此，相互关联的多学科研究旨在确定和描述疟疾的关键步骤， 传播周期，从而更好地了解寄生虫，宿主和媒介因素， 在密集的国家疟疾控制和消除方案的背景下，继续传播。这 这些知识将有助于开发新的方法来瞄准残留的传输袋。

项目成果

Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures.

• DOI: 10.1371/journal.pntd.0010633
• 发表时间: 2022-08
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8

Author Correction: The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density.

作者更正：潜伏的恶性疟原虫感染的时间动态和传染性与寄生虫密度的关系。

• DOI: 10.1038/s41467-019-10790-0
• 发表时间: 2019
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Slater,HannahC;Ross,Amanda;Felger,Ingrid;Hofmann,NatalieE;Robinson,Leanne;Cook,Jackie;Gonçalves,BronnerP;Björkman,Anders;Ouedraogo,AndreLin;Morris,Ulrika;Msellem,Mwinyi;Koepfli,Cristian;Mueller,Ivo;Tadesse,Fitsum;Gadisa,En
• 通讯作者: Gadisa,En

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.

• DOI: 10.1186/s12916-022-02285-5
• 发表时间: 2022-03-18
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Obadia T;Nekkab N;Robinson LJ;Drakeley C;Mueller I;White MT
• 通讯作者: White MT

Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens.

• DOI: 10.1371/journal.pcbi.1009801
• 发表时间: 2022-03
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Naung MT;Martin E;Munro J;Mehra S;Guy AJ;Laman M;Harrison GLA;Tavul L;Hetzel M;Kwiatkowski D;Mueller I;Bahlo M;Barry AE
• 通讯作者: Barry AE

Mobility evaluation by GPS tracking in a rural, low-income population in Cambodia.

• DOI: 10.1371/journal.pone.0266460
• 发表时间: 2022
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Pepey, Anais;Obadia, Thomas;Kim, Saorin;Sovannaroth, Siv;Mueller, Ivo;Witkowski, Benoit;Vantaux, Amelie;Souris, Marc
• 通讯作者: Souris, Marc