Evaluating Percentage-Based Reporting of Glucose-6-Phosphate Dehydrogenase (G6PD) Enzymatic Activity in a National Reference Laboratory: Assessment of Patient Eligibility for Plasmodium vivax Radical Cure Therapy

Abstract Objectives The World Health Organization recommends measurement of G6PD activity prior to initiation of 8-aminoquinolones for the treatment of P vivax malaria. An estimated 400 million people worldwide have G6PD deficiency, making them susceptible to hemolysis under oxidative stress. A new single-dose therapy (radical cure) for malaria with tafenoquine is contraindicated in patients with <70% normal G6PD activity due to its prolonged circulating half-life. However, most clinical laboratories report G6PD activity in units g/Hb or units/1012 RBC and do not provide percentage of normal activity, making potential eligibility determination challenging. Methods Using an IRB-exempt protocol, a limited data set of consecutive G6PD quantitative results was retrieved from the clinical laboratory’s enterprise data warehouse. Laboratory testing of these specimens was previously performed at 37°C using an automated enzymatic assay (Pointe Scientific) configured on a cobas c501 chemistry analyzer (Roche Diagnostics). Data were assembled to include adults age 18 to 89 years and excluded repeat results from the same patients as well as outliers. Conclusion The final data set included 52,216 results (female, 55.9%, n = 29,173; male, 44.1%, n = 23,043) from 47 US states. An adjusted male median (100% G6PD activity) was derived using an approach proposed by the Bangkok Workshop guidelines (Domingo et al., Malaria Journal, 2013), modified to more accurately differentiate bimodal peaks in population G6PD histograms. The laboratory-specific, adjusted male median was 12.7 U g/Hb and was similar to peak values derived from alternative curve-fitting approaches. Applying this median to gender-specific data sets, 5.4% of males and 3.8% of females were found to have <70% of normal activity (<8.9 U g/Hb). This study demonstrates the feasibility of percentage-based G6PD result reporting in adults; further studies will query percentage-based reporting in pediatric populations. Population-based medians will vary based on G6PD assay type and temperature and should be established by laboratories prior to percentage-based reporting.