Polymorphisms in Cytochrome P450 genes: implications for Plasmodium vivax malaria treatment in Brazil

Trans R Soc Trop Med Hyg. 2026 Mar 3;120(3):183-191. doi: 10.1093/trstmh/traf116.

Abstract

Plasmodium vivax is the most prevalent malaria parasite in Brazil, accounting for approximately 85% of annual malaria cases. Therapeutic failure in malaria has been associated with host genetic factors that influence drug metabolism. This study aimed to evaluate the impact of Cytochrome P450 gene polymorphisms on the treatment of Plasmodium vivax malaria in Brazil. A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Studies were screened based on title and abstract, duplicates were removed and articles published up to August 2024 were considered. Full-text eligibility and risk of bias assessments were performed. Allelic frequencies of the identified polymorphisms were extracted from the selected studies and visualised using pie charts. Of 296 studies retrieved, eight met the inclusion criteria. Most studies focused on the association between CYP2D6 polymorphisms and malaria treatment failure, employing a genotype-based approach to predict metaboliser phenotypes. Overall, the review revealed a lack of consensus regarding the relationship between Cytochrome P450 single nucleotide polymorphisms and antimalarial drug response. The potential implications of CYP450 genetic variability for therapeutic failure and treatment safety in Brazil are discussed.

Keywords: Brazilian Amazon; antimalarials; malaria; pharmacogenetics; public health.

Publication types

  • Systematic Review

MeSH terms

  • Antimalarials* / therapeutic use
  • Brazil
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 Enzyme System* / genetics
  • Humans
  • Malaria, Vivax* / drug therapy
  • Malaria, Vivax* / genetics
  • Plasmodium vivax* / drug effects
  • Polymorphism, Single Nucleotide

Substances

  • Antimalarials
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2D6