Malaria Network for the determination of pharmacokinetic and immunological profiles in the treatment of malaria by Plasmodium vivax in the Brazilian Amazon: researching biomarkers to predict therapeutic results

WHO recommends the association of chloroquine plus primaquine to cure infections caused by Plasmodium vivax. Studies report therapeutic failure of this association in endemic areas. One of the causes of therapeutic failure refers to the genetic factors of the host, among which the differential biometabolism of drugs, where the cytochrome P450 system plays an important role. Studies in populations from endemic areas have been characterizing allelic variants in the CYP450 genes/ CYP2 and CYP3 families that compromise the efficacy and toxicity of antimalarials. The frequencies of the variant alleles of the CYP2D6, CYP3A4, CYP3A5 and CYP2B6 genes will be quantified, in order to obtain the genotypes that determine different metabolization profiles. Blood samples from people infected with P. vivax, from the city of Porto Grande, Amapá, Brazilian Amazon will be tested. These patients will be treated and monitored according to the first-line scheme recommended by WHO and adopted by the Ministry of Health. Serum concentrations of chloroquine and primaquine will be determined by HPLC. The analysis of CYP genes will be by SnaPshot®. Gene expression of CYPs by qPCR during therapeutic follow-up. Twenty-two polymorphic loci of P. vivax will be investigated to estimate the multiplicity of infection and compare the profile of pre- and post-treatment infections. Cytokines will be analyzed by flow cytometry. Data will be evaluated using the statistical program SPSSH. Subsequently unified, such information may be incorporated into the strategies developed by the PNCM in susceptible areas, making them more specific and thus contributing to the effective treatment and control of malaria by P. vivax in the Brazilian Amazon.

Project details

Drug-based Strategies
P. vivax

May 2023

Brazil