An analysis of 48 Indonesian malaria patients examined CYP2D6 genotype-predicted phenotype, urinary primaquine-derived 5,6-orthoquinone, and methemoglobin. Intermediate metabolizers had lower metabolite concentrations, and the metabolite correlated positively with day-two methemoglobin.
Key findings
- Normal/ultra-rapid versus intermediate metabolizers had a 2.24-fold urinary-metabolite GMR (95% CI 1.26-3.98; p=0.01). Day-two methemoglobin GMR was 1.51 but nonsignificant (0.84-2.70; p=0.15). Each 1,000 ng/mL metabolite increase was associated with methemoglobin GMR 1.90 (1.37-2.63; p=0.0007).
Why this matters globally
Primaquine is central to preventing vivax relapse but response varies. Accessible markers could aid trial interpretation and precision dosing if linked safely to efficacy and hemolysis outcomes.
Thai researcher contribution
A MORU-affiliated researcher contributed to an Indonesian-Australian-Oxford malaria pharmacogenetics network. Patients and samples were Indonesian, not Thai.
Limitations to consider
The sample is 48 with potentially small phenotype strata. Phenotype is genotype-predicted, methemoglobin reflects pharmacology and oxidative toxicity rather than efficacy, relapse outcomes are absent, G6PD context is not stated in the abstract, and associations do not define causal cutoffs.
Verify the original sources
Antimicrobial Agents and ChemotherapyRead the original article↗DOI: 10.1128/aac.00539-26