MRC FAPESP: Defining the role of the hematopoietic parasite reservoir in Plasmodium vivax infection and pathology

间日疟原虫是分布最广泛的疟疾寄生虫，也是一个主要的公共卫生负担。最近的研究表明，大多数寄生虫存在于血液循环之外，这使得追踪和瞄准它们变得困难。我们已经证明，特别是骨髓是一个未被充分认识的水库，它支持间日疟原虫的生长和分化到传播阶段。类似的研究也报道了脾脏中主要的寄生虫积聚。基于这些发现，我们假设骨髓和脾脏的造血生态位是感染期间寄生虫的主要储存库，并驱动疾病的严重程度。在这个雄心勃勃的研究计划中，我们将分析巴西流行地区自然暴露患者的一系列队列中受感染的骨髓和脾脏组织。我们将对被隔离和循环的寄生虫和宿主细胞群进行组织学、分子和表型表征，系统地调查和量化骨髓和脾脏在寄生虫感染、传播、诊断和病理中的作用。因此，这项工作将为正在进行的全球消除疟疾运动提供急需的见解和关键工具。

Plasmodium vivax is the most widely distributed malaria parasite and a major public health burden. Recent studies suggest that the majority of parasites is present outside of circulation, making it difficult to track and target them. We have demonstrated that bone marrow in particular represents an under-appreciated reservoir which supports P. vivax growth and differentiation to transmission stages. Parallel studies have also reported major parasite accumulation in the spleen. Based on these findings we hypothesize that the haematopoietic niche of bone marrow and spleen represents the main parasite reservoir during infection and drives disease severity. In this ambitious research program, we will analyze infected bone marrow and spleen tissue from a series of cohorts of naturally exposed patients in endemic areas in Brazil. We will perform histological, molecular and phenotypic characterization of sequestered and circulating parasite and host cell populations to systematically investigate and quantify the role of bone marrow and spleen for parasite infection, transmission, diagnosis and pathology. This work will thus contribute much needed insights and critical tools for the ongoing global malaria elimination campaign.