Dados do Trabalho

Título

Characterization of recurrent episodes of vivax malaria and identification of predictive biomarkers of relapses.

Introdução

Plasmodium vivax is the leading cause of malaria outside of Africa and its biology represents a challenge to malaria eradication. Hypnozoites are latent undetectable forms that cause malaria relapses from the liver into the bloodstream and are considered a barrier for its control and elimination by maintaining residual transmission. The understanding of the biological features of hypnozoite carriers is helpful to the identification of individuals harboring these clinically silent forms.

Objetivo (s)

Hence, our goal is to identify a suitable molecular profile as a predictive biomarker of relapses.

Material e Métodos

As a proof-of-concept, 72 malaria vivax patients were followed in a longitudinal cohort at FMT-HVD in Manaus and proteomic MALDI-TOF mass spectrometry analysis revealed a differential expression of peaks tightly associated with recurrence episodes. Moreover, non-recurrent individuals showed increased response IgG intensity to P. vivax blood antigens in comparison to recurrent individuals. These results encouraged us to investigate the biomarker profile of vivax malaria patients, as they were monitored for recurrences from admission until ninety days after their inclusion. Up to now, 179 patients have been enrolled in the study and the recurrence rate reported between 31-90 days (mean of 71 days) is 15,6% (28 recurring patients). Ultimately, our purpose is to characterize this cohort according to a panel of biomarkers including antibody response to P. vivax antigens, metabolomic and proteomic analysis, biomass (PvLDH), and miRNA sequencing. Furthermore, micro-satellite and CYP2D6 genotyping will be used as criteria for relapse identification. As reference of a true relapse profile, we will analyze samples from vivax malaria recurring individuals recruited outside the endemic transmission area.

Resultados e Conclusão

The results generated here will be useful to the characterization of a signature-biomarker to identify individuals with a higher risk of harboring hypnozoites which could be a surveillance tool in an intervention setting.

Palavras-chave

Keywords: Malaria, Plasmodium vivax, hypnozoites, relapse.

Agradecimentos

Financial support: FAPESP, CNPq, and Bill and Melinda Gates Foundation.