Abordagem clínico-laboratorial e dos polimorfismos nos genes PVMDR-1 e PVCRT-O como indicadores do prognóstico de pacientes com malária vivax

Abstract

In recent years, Plasmodium vivax malaria has shown an increasing occurrence of cases with complications and resistance to chemotherapy treatment. Although there are clinical and laboratory markers recommended by the WHO for classification of severity, it is necessary to identify routine laboratory parameters that best characterize the acute phase of the disease and that can serve as a tool for assessing the prognosis. In addition, P. vivax genetic markers that demonstrate the susceptibility of infection and pathogenesis of these parasites can also contribute to determine the prognosis of the disease. To this end, a seven-year open cohort study was carried out in which we followed 189 patients with malaria due to P. vivax from the Brazilian Amazon. A total of 42 different biochemical and hematological parameters frequently tested in the clinical routine were evaluated in the acute and convalescent phase, and polymorphisms in the PvMDR-1 and PvCRT-o genes were investigated. Altogether, 22 parameters were associated with the acute phase, the 10 most relevant being C-reactive protein, indirect bilirubin, neutrophil / lymphocyte ratio, total bilirubin, α-1-acid glycoprotein and direct bilirubin, which were elevated in this phase. The parameters platelet, lymphocytes, platelets and eosinophils, were significantly decreased in the acute phase. These 10 parameters reached normality in the convalescence phase and have the potential to assist the medical team in assessing the prognosis of patients infected with P. vivax. The T958M and F1076L mutations of the PvMDR-1 gene had a frequency of 3.3% and 4.2% respectively, and primo-infected patients had a 17 times greater chance of being infected with protozoa with the T958M mutation. Regarding PvCRT-o, the C393T and T786C polymorphisms had a frequency of 14.2% and 3.3%, respectively, and self-declared white patients had a 3.1 times greater chance of being infected with protozoa with the C393T polymorphism. In addition, patients with this PvCRT-o polymorphism had lower concentrations of C-reactive protein, which indicates a better prognosis for these patients. These data demonstrate that laboratory and genetic parameters can be useful tools in the prognosis of patients with vivax malaria.