A 32-year-old man from rural Maharashtra presents with fever, chills, and headache for 3 days. Blood smear examination confirms Plasmodium vivax malaria. He is started on chloroquine. Which is the most common cause of chloroquine resistance in P. vivax malaria in India?

Explanation

## Chloroquine Resistance in P. vivax **Key Point:** Chloroquine resistance in P. vivax is primarily mediated by mutations in the pvmdr1 gene (Plasmodium vivax multidrug resistance 1) and alterations in drug transporter proteins, particularly the P. vivax chloroquine resistance transporter (PvCRT). ### Mechanism of Resistance The pvmdr1 gene encodes a P-glycoprotein homologue that functions as a drug transporter. Mutations in this gene reduce drug accumulation within the parasite, decreasing chloroquine bioavailability at its site of action (the parasite's digestive vacuole). **High-Yield:** The most common mutation associated with chloroquine resistance in P. vivax is the Y976F mutation in pvmdr1, which is widespread across India and Southeast Asia. ### Why This Matters Clinically | Feature | P. vivax Resistance | P. falciparum Resistance | |---------|-------------------|------------------------| | Primary gene | pvmdr1, PvCRT | pfmdr1, PfCRT | | Mechanism | Drug efflux | Drug efflux, reduced uptake | | Geographic prevalence | India, SE Asia | Widespread, Africa | | Clinical consequence | Treatment failure, relapse | High mortality if untreated | **Clinical Pearl:** In areas with documented chloroquine-resistant P. vivax (CRPV), artemisinin-based combination therapy (ACT) or primaquine with artesunate is preferred over chloroquine monotherapy. **Mnemonic:** **PvMDR1** = **P**lasmodium **v**ivax **M**ulti**D**rug **R**esistance gene (chromosome 5) — the culprit in vivax chloroquine resistance.