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 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, and included G6PD screening, targeting high dose primaquine and early clinical review. 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 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 Indonesias 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. The ICER reduced when the societal perspective was included, with NPT cost-effective in Indonesia overall ($2,261/DALY averted) and in Papua ($675/DALY averted). The risk of P. vivax recurrence and intervention costs were the most influential parameters on the ICER. Overall, NPT was between the 1-3x GDP per capita cost-effectiveness thresholds in Indonesia; however, cost-effectiveness varied significantly across settings, indicating that NPT may not be an optimal use of resources in areas with low incidence.