CYP2D6 polymorphisms and risk of Plasmodium vivax relapses after treatment with chloroquine and primaquine in Brazil and Colombia

Despite recent advances towards the elimination of malaria in the Americas, important foci of transmission persist in the Amazon and on the Pacific and Atlantic coasts of South and Central America. Plasmodium vivax, responsible for almost 80% of cases, has a unique ability to remain dormant in the liver, in the form of hypnozoites, reactivating weeks or months after the primary infection to cause relapses. Primaquine (PQ), the only widely available drug effective against hypnozoites, is an inactive prodrug whose effect requires biotransformation by the CYP2D6 enzyme of the cytochrome P450 system (CYP). The hypothesis is that individuals with low activity variants of CYP2D6 treated with chloroquine (CQ) combined with PQ present a high risk of P. vivax relapses in the main endemic areas of South America, with important consequences for Public Health. To test this hypothesis, genotyping CYP2D6 polymorphisms was envisioned in: (a) participants from a cohort of 2000 individuals exposed to ongoing malaria in the Juruá Valley, Brazilian Amazon, and (b) participants from a recent therapeutic efficacy study of Supervised CQ -PQ on the Caribbean coast of Colombia, which showed a P. vivax relapse rate of 24.1% over 6 months of follow-up. The primary study endpoints are: (a) the incidence of laboratory-confirmed vivax malaria, according to levels of CYP2D6 activity, among participants in the Brazilian cohort followed for two years, and (b) the time elapsed until the first relapse, among study participants colombian with different levels of CYP2D6 activity followed for 180 days after treatment with CQ-PQ.

Project details

Drug-based Strategies
P. vivax

Feb 2021 — Jan 2023

Brazil
Colombia