Primaquine and G6PD deficiency — DTM&H MCQ

Correct answer: C — Risk of haemolytic anaemia in G6PD-deficient individuals

The correct answer is C, risk of haemolytic anaemia in G6PD-deficient individuals. Primaquine is an 8-aminoquinoline that generates oxidative metabolites in red cells, and in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency this triggers acute, dose-dependent, potentially severe haemolysis. G6PD deficiency is common (often 5 to 20 percent prevalence) across many vivax-endemic populations, and UK malaria treatment guidance specifically warns that primaquine should be avoided or given only with expert supervision and G6PD testing because of this haemolysis risk. In a mass drug administration setting there is no time or infrastructure to test every recipient's G6PD status before dosing, so the safety barrier is population-level, not a resistance or supply problem, making this the operational bottleneck for scaling up radical cure. Why the other options are wrong: D. High cost of primaquine in resource-limited settings: primaquine is an old, cheap, off-patent drug; cost is not the limiting factor for mass programmes. E. Primaquine resistance in P. vivax hypnozoites: primaquine remains effective against hypnozoites when adequately dosed; true resistance is not established as the operational barrier, unlike documented chloroquine resistance in blood-stage parasites. A. Requirement for intravenous administration: primaquine is given orally, which is precisely why it is otherwise attractive for community-based mass programmes. B. Teratogenicity limiting use in women of childbearing age: primaquine is contraindicated in pregnancy, but this affects only a subgroup and is a manageable exclusion criterion, not the principal barrier to whole-population deployment, unlike the unpredictable G6PD-related haemolysis risk affecting a large, often unscreened, proportion of any endemic population. Key point: without prior G6PD testing, primaquine mass administration risks unpredictable severe haemolysis, making population screening the rate-limiting step for scale-up, not cost, resistance, route or pregnancy alone.

Reference: UK Malaria Treatment Guidelines 2016 (Journal of Infection; PHE/UK malaria treatment guidelines writing group), recommendation 21: primaquine should be avoided or given with caution under expert supervision in G6PD deficiency due to risk of severe haemolysis. https://www.journalofinfection.com/article/S0163-4453(16)00047-5/pdf