Last Updated: 07/10/2025
Plasmodium vivax: a cryptic infection that challenges the challenge of malaria elimination
Objectives
The main aim of to study is to test the hypothesis that, in addition to hypnozoites, P. vivax has developed cryptic infections in the bone marrow and spleen and that exosomes in natural P. vivax infections act as intercellular communicators that facilitate the adhesion and sequestration of parasites in these organs. In addition, the circulating extracellular vesicles of asymptomatic hypnozoite carriers contain specific proteins for these forms, enabling the discovery of biomarkers of latent infections in the liver.
To test this hypothesis, the specific objectives are:
- the molecular identification and functional validation of parasite ligands and host receptors in human bone marrow and spleen through global transcription analysis and CRISPR/CAS9 technology;
- the construction of humanized mouse models to demonstrate the existence of such cryptic niches in these organs in vivo; and
- the discovery of hypnozoite biomarkers and the development of a POC microfluidic device for their validation.
Plasmodium vivax is the most widely distributed parasite in the world that causes human malaria. Because of some of its unique biological characteristics, such as its preference for invading reticulocytes and its ability to develop dormant forms in the liver, experts agree that achieving its elimination requires a better understanding of its fundamental biology and the discovery of biomarkers for asymptomatic liver infections.
Over the past three years, the research team has gathered strong evidence suggesting that hypnozoites—the latent parasitic forms in the liver responsible for clinical relapses—are not the only source of cryptic infections in this species. Furthermore, the use of humanized mouse models could pave the way for the discovery of biomarkers for latent liver infections.
The investigators have demonstrated that exosomes, extracellular vesicles of endocytic origin secreted by reticulocytes in natural infections, contain parasite proteins and signal to human spleen fibroblasts, facilitating the cytoadherence of infected reticulocytes. They have also observed the presence of parasites in the bone marrow of patients during clinical paroxysms. Finally, the research group has shown that circulating extracellular vesicles in plasma from a humanized mouse model that supports hypnozoite development contain parasite proteins.
Jan 2019
$243,801
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