Last Updated: 31/07/2024
Characterization of vivax malaria recurrence episodes and identification of biomarkers predictive of disease relapse
Objectives
*Original in Portuguese: Caracterização de episódios de recorrência de Malária vivax e identificação de biomarcadores preditivos de recaídas da doença
This project aims to identify biomarkers that can predict relapse episodes of Plasmodium vivax malaria through an omics approach and antibody response.
Plasmodium vivax is the most prevalent species that causes human malaria outside Africa and its biology poses a challenge to eradicating the disease. The characteristics of this species include the ability to cause recurrences, which correspond to the reappearance of clinical signs and peripheral parasitemia weeks to months after diagnosis and treatment of the initial infection. Recurrences can have several causes, among which the reactivation of latent hepatic forms of the parasite, the hypnozoites, stands out, which is called relapse. Understanding the biology of these forms, as well as the characteristics of the hypnozoite-carrying host, are determining factors in controlling this disease. To this end, samples are being collected from patients with vivax malaria admitted to the Tropical Medicine Foundation (Manaus-AM) who have or have not had recurrences. In addition to proteomics and metabolomics analyses, the project will evaluate the clinical data of these patients, as well as parasitemia, parasite load and parasite biomass. The miRNA, cytokine and chemokine profile will also be checked. To date, more than 150 patients have been recruited, with a frequency of recurrences of 15.6% that occurred between 31-90 days. Preliminary principal component analysis (PCA) of MALDI-TOF mass spectrometry data revealed a distinct proteomic profile of plasma from patients with or without recurrence on the day of the first episode of vivax malaria. Furthermore, individuals without recurrence showed a greater intensity of IgG antibody response to P. vivax blood antigens when compared to those who recurred. Importantly, in parallel microsatellite analyzes and CYP2D6 genotyping will be performed, as well as chloroquine dosage as a criterion for identifying relapses. However, as a genuinely true reference for relapses, we will also analyze samples of individuals who presented recurrences outside the malaria endemic area admitted to FIOCRUZ-RJ. The results obtained in this study will be useful to identify a signature of biomarkers capable of detecting individuals at high risk of experiencing relapse episodes, which can be used in epidemiological surveillance and as a guiding tool for intervention.
Nov 2023 — Oct 2026
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