Cost-effectiveness of a package to ensure safe prescription of 7-day high-dose primaquine for the radical cure of Plasmodium vivax in Indonesia

The radical cure of Plasmodium vivax requires treatment of the dormant liver stages with either primaquine or tafenoquine, but widespread implementation of this policy is constrained by the risk of severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. A revised case-management package, ‘New Primaquine Treatment’ (NPT), was designed to support safe radical cure in Indonesia. The package includes G6PD screening, targeting high-dose primaquine and an early clinical review to encourage full adherence to a complete course of treatment providing no early signs of adverse reactions. A decision-tree model was constructed using individual-level data from a study that treated patients with 7mg/kg primaquine according to their G6PD activity: primaquine administered over 7 days (G6PD normal individuals), 14 days (individuals with intermediate G6PD deficiency), or 8 weeks (if severely G6PD deficient). The model incorporated costs, adverse events, and the risk of P. vivax recurrence over a six-month time horizon. A business-as-usual comparator was created using historical P. vivax recurrence data for Indonesia overall and the three provinces separately. The primary outcome was disability-adjusted life-years (DALYs) averted. Costs were analyzed from health system and societal perspectives, and incremental cost-effectiveness ratios (ICERs) were compared with Indonesia’s Health Technology Assessment recommended willingness-to-pay thresholds of 1 and 3 gross domestic product per capita (US$4,925 and$14,475). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. Overall, NPT averted 0.0011 DALYs per patient with an incremental cost of US$7.40 per patient from a health system perspective. This resulted in an ICER of US$6,636 per DALY averted which was not cost-effective at the $4,925 threshold. Cost-effectiveness varied across settings: from US$5,098 per DALY averted in Papua to US$20,051 per DALY averted in southern Sumatra and US$80,825 per DALY averted in northern Sumatra, largely due to varied endemicity and case numbers. However, when the societal perspective was included, the ICER reduced significantly resulting in NPT being cost-effective overall in Indonesia ($2,261/DALY averted), and this was particularly apparent in highly endemic Papua ($675/DALY averted). The risk of P. vivax recurrence and intervention costs were the most influential parameters on the ICER. Overall, NPT fell between the 1-3x GDP per capita cost-effectiveness thresholds in Indonesia; however, cost-effectiveness varied significantly across settings, indicating that NPT should be prioritized for areas with high incidence of P. vivax malaria.