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How CYP2D6 Polymorphism Modulates the Community-Wide Risk of Plasmodium vivax Infection: A Panel Study in Amazonian

Maria Carolina Silva de Barros Puça1,2, Isabela Marques Naziazeno1, Viviane Cristina Fernandes Dos Santos1

  • 1Molecular Biology and Malaria Immunology Research Group, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil.

The Journal of Infectious Diseases
|August 19, 2025
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Summary
This summary is machine-generated.

Individuals with impaired CYP2D6 enzyme activity show different Plasmodium vivax malaria infection patterns. This suggests CYP2D6 influences malaria immunity and infection dynamics in endemic regions.

Keywords:
Plasmodium vivaxCYP2D6malariaprimaquinerisk of infection

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Area of Science:

  • Pharmacogenomics
  • Infectious Disease Epidemiology

Background:

  • The CYP2D6 enzyme is crucial for metabolizing primaquine, a key drug for Plasmodium vivax malaria radical cure.
  • Impaired CYP2D6 activity is linked to higher relapse risk, but its broader impact on infection dynamics remains unclear.

Purpose of the Study:

  • To investigate the hypothesis that impaired CYP2D6 activity accelerates partial immunity development due to inefficient hypnozoite clearance.
  • To explore the role of CYP2D6 in shaping Plasmodium vivax infection dynamics and host immunity.

Main Methods:

  • A community-based study followed approximately 1,300 individuals genotyped for CYP2D6 over 4 years.
  • Molecular diagnostics were used for repeated assessment of P. vivax, enabling detection of submicroscopic and asymptomatic infections.

Main Results:

  • Children with impaired CYP2D6 activity had a higher frequency of P. vivax infections than those with normal activity.
  • P. vivax prevalence increased in adolescents with normal CYP2D6 activity, while adults with impaired activity showed lower parasite densities.

Conclusions:

  • CYP2D6 activity significantly influences Plasmodium vivax infection patterns and the development of malaria immunity.
  • These findings highlight the pharmacogenetic aspect of malaria control and host-parasite interactions.