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，大多数寄生虫都存在于循环系统之外，因此很难追踪和靶向它们。我们已经证明，骨髓特别代表了一个未被充分认识的水库，支持间日疟原虫生长和分化到传播阶段。平行研究还报告了脾脏中的主要寄生虫蓄积。基于这些发现，我们假设骨髓和脾脏的造血生态位代表了感染过程中的主要寄生虫库，并驱动了疾病的严重程度。在这项雄心勃勃的研究计划中，我们将分析来自巴西流行地区一系列自然暴露患者的受感染骨髓和脾脏组织。我们将对隔离和循环的寄生虫和宿主细胞群体进行组织学、分子和表型表征，以系统地研究和量化骨髓和脾脏在寄生虫感染、传播、诊断和病理学中的作用。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重要工具。

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.