Last Updated: 31/01/2025
MRC-FAPESP: Defining the function of the hematopoietic reservoir of parasites in infection and pathology caused by Plasmodium vivax
Objectives
*Original in Portuguese: MRC-FAPESP: Definindo a função do reservatório hematopoiético de parasitas na infecção e patologia causadas por Plasmodium vivax
This ambitious research program will analyze infected bone marrow and spleen tissue from a series of cohorts of naturally exposed patients in endemic areas in Brazil. Histological, molecular and phenotypic characterization of sequestered and circulating parasite and host cell populations will be performed to systematically investigate and quantify the role of bone marrow and spleen for parasite infection, transmission, diagnosis and pathology.
Plasmodium vivax (P. vivax) places a heavy disease burden across endemic regions worldwide and presents a major challenge for malaria eradication. Recent studies from our laboratories and others have demonstrated that the extravascular bone marrow niche and potentially the spleen represent a major tissue reservoir for parasite proliferation and transmission stage maturation across Plasmodium spp. lineages, with significant implications for malaria diagnosis and treatment success. P. vivax is restricted to invasion of the youngest red blood cells, known as immature reticulocytes, which originate in the bone marrow. This restriction results in a distinct and poorly understood biology that we believe has precluded previous efforts to establish in vitro parasite culture and systematic study of P. vivax. Importantly, P. vivax elicits a potent host response and causes severe and fatal manifestations at much lower parasitaemia than P. falciparum, suggesting that P. vivax restriction to host cells enriched in the hematopoietic niche of BM and spleen could induce alterations in host homeostasis such as anaemia, lymphopenia, thrombocytopenia and splenomegaly. This collaborative proposal will employ for the first time a systematic investigation of the biology of the P. vivax reservoir in BM and spleen and its role in disease pathogenesis, infection and transmission in a series of cohorts of patients in Brazil. This project will characterize parasite and host biology in infected tissues and investigate their behaviour ex vivo using a series of cutting edge technologies and in collaboration with world leading experts. The proposed work will thus close a major knowledge gap in our understanding of P. vivax biology and pathogenesis and provide critical tools for the development of new P. vivax control measures to support the ongoing malaria elimination agenda.
CAPES project detailsUKRI project detailsFAPESP project details
May 2022 — May 2026
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