Characterization of recurrent episodes of Vivax Malaria and identification of predictive biomarkers for disease relapse

• Grant number: 23/08454-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2023
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: João Pedro da Cunha Tavares
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, AP.TEM

Abstract

Plasmodium vivax is the leading cause of malaria outside of Africa and its biology represents a challenge to malaria eradication. Among the characteristics of this species, it includes the ability to cause recurrences, which correspond to the reappearance of clinical signs and peripheral parasitemia weeks to months after the diagnosis and treatment of the infection. Recurrences can have various causes, among which the reactivation of latent hepatic forms of the parasite, known as hypnozoites, stands out, which is referred to as relapse. Understanding the biology of these forms, as well as the host characteristics, are determining factors in controlling this disease. Therefore, through an Omics approach and antibody response, we intend to identify a set of predictive biomarkers for relapses. For this purpose, samples are being collected from patients admitted to FMT-HVD (Manaus-AM) with vivax malaria, who have experienced recurrences or not. In addition to proteomic and metabolomic analyses, we will evaluate the clinical data of these patients, as well as parasitemia, parasite load, and parasite biomass. The profiles of miRNA, cytokines, and chemokines will also be examined. So far, more than 150 patients have been recruited, with a recurrence/relapse frequency of 15.6%, occurring between 31-90 days. Preliminary principal component analysis (PCA) of MALDI-TOF mass spectrometry data revealed a distinct proteomic profile in the plasma of patients with or without recurrence on the day of the first vivax malaria episode. Furthermore, individuals without recurrence showed a higher intensity of IgG antibody response to P. vivax blood antigens compared to those who experienced relapses. Importantly, we will also perform microsatellite analysis and genotyping of CYP2D6, as well as chloroquine dosage as criteria for identifying relapses. Additionally, as a reference for genuinely true relapses, we will also analyze samples from individuals who experienced recurrences outside the malaria-endemic area, admitted to FIOCRUZ-RJ. The results obtained in this study will be useful in identifying a biomarker signature capable of detecting individuals at high risk of experiencing relapse episodes, which can be used in epidemiological surveillance and as a guiding intervention tool. This project is funded by the São Paulo Research Foundation - FAPESP (Processes 2021/04632-8 and 2017/18611-7), the Bill & Melinda Gates Foundation (Process 5597), and the National Council for Scientific and Technological Development - CNPq (Process 442946/2019-8). (AU)