| Texto completo | |
| Autor(es): |
Puca, Maria Carolina Silva de Barros
;
Naziazeno, Isabela Marques
;
dos Santos, Viviane Cristina Fernandes
;
Rodrigues, Priscila Thihara
;
Calil, Priscila Rodrigues
;
Ladeia, Winni Alves
;
Gil, Jose Pedro
;
Ferreira, Marcelo Urbano
;
Nobrega De Sousa, Tais
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Infectious Diseases; v. 232, n. 4, p. 9-pg., 2025-09-03. |
| Resumo | |
Background The CYP2D6 enzyme plays a critical role in the metabolism of primaquine, the most widely used drug for the radical cure of Plasmodium vivax malaria. Impaired CYP2D6 activity has been associated with an increased risk of relapse. However, the overall impact of CYP2D6 on infection dynamics is still not fully understood. We hypothesized that individuals with impaired CYP2D6 activity develop partial immunity more rapidly due to the ineffective clearance of hypnozoites.Methods To test this hypothesis, we conducted a community-based study involving similar to 1300 individuals genotyped for CYP2D6 and assessed repeatedly for P. vivax using molecular diagnosis. This approach allowed us to detect and monitor submicroscopic and asymptomatic infections over a 4-year follow-up period.Results In our cohort, children with impaired CYP2D6 activity exhibited a higher frequency of P. vivax infections compared with those with normal enzyme activity. This pattern changed during the second decade of life, as the prevalence of P. vivax infection increased in adolescents with normal enzyme activity (P = .0008, Generalized additive mixed model). Consistent with this, parasite densities were lower in adults with impaired CYP2D6 activity compared with younger individuals with normal enzyme activity (P = .0383, Linear mixed model).Conclusions These findings underscore the potential role of CYP2D6 in shaping infection dynamics and malaria immunity in endemic areas. This study investigated whether individual variation in primaquine metabolism influences susceptibility to P. vivax by affecting hypnozoite clearance and immunity acquisition, revealing higher infection rates in children with impaired CYP2D6 activity and age-dependent shifts in infection patterns and parasite densities. (AU) | |
| Processo FAPESP: | 20/03611-4 - Polimorfismos em CYP2D6 e risco de recidivas de Plasmodium vivax após o tratamento com cloroquina e primaquina no Brasil e na Colômbia |
| Beneficiário: | Marcelo Urbano Ferreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/11963-3 - Variação individual no risco de malária: causas e consequências em populações amazônicas |
| Beneficiário: | Marcelo Urbano Ferreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 16/18740-9 - Bases científicas para a eliminação da malária residual na Amazônia Brasileira |
| Beneficiário: | Marcelo Urbano Ferreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |