Genetic study of host-parasite interactions associated with Malaria susceptibility

Abstract

Malaria remains the most important parasitic disease worldwide due to its high morbidity and mortality and its wide geographical distribution in tropical regions. In Brazil, this disease is mainly caused by Plasmodium vivax species and more than 99% of cases occur in the Legal Amazon region. Genetic components of the parasite and the host can influence the infection course, such as the presence of a polymorphism that inhibits the expression of the Duffy antigen, a molecule used as the traditional route of entry for P. vivax into erythrocytes. Furthermore, there are still several gaps in knowledge regarding the impact of other human deficiencies, such as G6PD deficiency and beta thalassaemia, on vivax malaria. In view of this, this study aims to characterise genetic factors in the parasite-host interaction involved in susceptibility to vivax malaria in a highly endemic region of the Brazilian Amazon. For this purpose, blood samples and epidemiological and clinical data from 300 participants in studies conducted in the Juruá Region (Acre State) between 2013 and 2021 will be used. In addition to these, new samples will be collected in the same region in 2025, totaling 600 participants that will be included in the final analysis. For ACKR1 and G6PD gene sequencing, third generation sequencing technology will be used with a portable platform from Oxford Nanopore Technology, the MinION. The parasitemia of infected individuals will be assessed by qPCR and the levels of pro- and anti-inflammatory cytokines will be measured by flow cytometry. The results obtained will contribute not only to understanding the components that can influence the disease susceptibility, but also for predicting the effectiveness of new control and treatment methodologies. (AU)