Hubbard Alfred, Solares Edwin, Bradley Lauren, Jeang Brook, Yewhalaw Delenasaw, Janies Daniel, Lo Eugenia, Yan Guiyun, Hemming-Schroeder Elizabeth
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Computer Science and Engineering, UC San Diego, San Diego, California, USA.
medRxiv. 2025 May 2:2025.04.30.25326751. doi: 10.1101/2025.04.30.25326751.
malaria research has yet to fully benefit from the advances in genomic surveillance that have revolutionized epidemiology. Closing this gap is critical because genomic tools are necessary to achieve certain malaria control program objectives: 1) they allow monitoring of the spread of drug resistance and thus selection of therapeutic drugs based on local prevalence of resistance; 2) they permit classification of infections as local or imported, enabling more precise targeting of control resources; and 3) they can distinguish reinfection, recrudescence, and relapse, a necessity for conducting therapeutic efficacy studies. To achieve these objectives, microhaplotype marker panels that allow powerful genotyping of polyclonal infections are needed. A handful of such panels have been published for , but they may be limited to certain geographic areas. We here present a Globally-applicable Amplicon Panel for (PvGAP) designed to maximize discriminatory capability between geographic regions. PvGAP has 80 high diversity targets suitable for population genomics and eight targets of specific epidemiological interest, such as putative markers of drug resistance. We demonstrate PvGAP achieves robust amplification with field data and that it clearly distinguishes samples from different locations both at a regional and global scale. PvGAP is ready for broad application that can support powerful and comprehensive studies of malaria genomic epidemiology.
疟疾研究尚未充分受益于基因组监测方面的进展，而这些进展已经彻底改变了流行病学。弥合这一差距至关重要，因为基因组工具对于实现某些疟疾控制项目目标是必要的：1）它们可以监测耐药性的传播，从而根据当地耐药性流行情况选择治疗药物；2）它们能够将感染分类为本地感染或输入性感染，使控制资源的靶向更精确；3）它们可以区分再感染、复发和复燃，这是进行治疗效果研究的必要条件。为实现这些目标，需要能够对多克隆感染进行高效基因分型的微单倍型标记面板。已经发表了一些这样的面板，但它们可能仅限于某些地理区域。我们在此展示了一种全球适用的疟原虫扩增子面板（PvGAP），其设计目的是最大限度地提高不同地理区域之间的区分能力。PvGAP有80个适用于群体基因组学的高多样性靶点以及八个具有特定流行病学意义的靶点，例如假定的耐药性标记。我们证明PvGAP利用现场数据实现了稳健的扩增，并且在区域和全球范围内都能清晰地区分来自不同地点的样本。PvGAP已准备好广泛应用，可支持对疟疾基因组流行病学进行有力且全面的研究。
