Abstract
Plasmodium vivax (P. vivax) can lead to severe hematological complications, including anemia and thrombocytopenia, which may require hospitalization. This prospective observational study investigated the adaptive immune response in pediatric P. vivax malaria, focusing on sustained IFN-γ production in CD4(+) and CD8(+) memory T cells as markers of immune protection. Conducted at the Dr. Heitor Vieira Dourado Tropical Medicine Foundation (FMT-HVD) in the Western Brazilian Amazon, peripheral blood mononuclear cells (PBMCs) were collected from 25 children aged 1-16 years at diagnosis (D0, acute phase) and 90 days post-treatment (D90, convalescent phase). PBMCs were stimulated ex vivo with the conserved P. vivax antigen, the 19 kDa fragment of the C-terminal region of merozoite surface protein-1 (PvMSP1(19)), and intracellular production of IFN-γ was quantified in memory T cells (CD3(+)CD4(+)CD45RO(+) and CD3(+)CD8(+)CD45RO(+) T cells) by flow cytometry. Individuals whose cells specifically produced IFN-γ against PvMSP1(19) on both D0 and D90 were classified as responders, while those who responded in only one phase or in neither were classified as nonresponders. Responders, whose CD3(+)CD4(+)CD45RO(+) T cells exhibited sustained IFN-γ response against PvMSP1(19) demonstrated lower parasite density as well as improved normalization of hemoglobin levels and recovery of platelet counts. These results confirm the role of this response as acquisition of immunity. PvMSP1(19) antigen emerges as a promising marker of sustained immunity, though larger studies are required to evaluate its long-term impact on recovery and outcomes. These findings underscore the critical role of IFN-γ-producing memory T cells in controlling parasitemia and mitigating anemia and thrombocytopenia in pediatric P. vivax malaria.