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Last Updated: 03/08/2023
Project Zoonotic Malaria in the Brazilian Atlantic Forest: Study of the genetic variability of molecules involved in the process of invasion of erythrocytes by P. simium
Objectives
*Original title in Portuguese: Projeto Malária Zoonótica na Mata Atlântica Brasileira: Estudo da variabilidade genética das moléculas envolvidas no processo de invasão dos eritrócitos pelo P. simium
This project sets to analyse the genes involved in the process of invasion of erythrocytes by P. simium isolated from naturally infected non-human primates (NHPs).
In Brazil, most human cases of malaria occur in the legal Amazon. However, autochthonous cases occasionally occur in the Atlantic Forest regions of South and Southeast Brazil. It has recently been demonstrated that these cases are the result of zoonotic transmission of Plasmodium simium infecting non-human primates (NHPs). Two species of malaria parasites are able to infect PNHs in the Atlantic Forest, Plasmodiium brasilianum and P. simium, closely related to the parasites that cause human malaria, P. malariae and P. vivax, respectively. Binding and invasion of red blood cells by P. simium is mediated by two major families of genes expressed in merozoites: Duffy binding proteins (DBPs) and reticulocyte binding proteins (RBPs). In P. vivax, DBPs bind to the Duffy Chemokine Antigen Receptor (DARC), which is present on both host normocytes and reticulocytes, and RBPs are known to restrict binding of P. vivax to reticulocytes. Despite the importance of this parasite due to its zoonotic character, relatively little is known about its evolutionary history and the adaptations that these parasites have undergone to allow them to be able to parasitize different hosts and vectors. Studies on the genetic diversity of the DARC receptor in Neotropical primates are also scarce. The objective of this project is to clarify these topics through the analysis of the genes involved in the process of invasion of erythrocytes by P. simium isolated from naturally infected PNHs. Initially, in order to achieve this objective, it will be necessary to make a differential diagnosis of infection by P. simium, for which a methodology patented by the group will be used, a Nested/PCR RFLP. Then, the amplification and sequencing of proteins related to the process of invasion of P. simium in erythrocytes from different hosts will be carried out. In this way, it will be possible to clarify the evolution and adaptation of these parasites in different hosts and contribute to the definition of public policies for the prevention and control of Zoonotic malaria.
Mar 2022 — Sep 2023