Clinical performance validation of the STANDARD G6PD test: A multi-country pooled analysis

Abstract

Introduction Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. Methods and findings Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%–100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%–85.4%) for females with intermediate activity between 30%–70%. Specificity was 98.1% (95% CI 97.6%–98.5%) and 92.8% (95% CI 91.6%–93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%–99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%–100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. Conclusions The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Diagnostic accuracy of the Point-of-Care Standard G6PD test™ (SD Biosensor) for Glucose-6-phosphate dehydrogenase deficiency: a systematic review of the literature

“…However, the same study found that the reliability of the test was poor in discriminating between intermediate and low G6PD activities in lyophilized samples (27), emphasizing the need for further research in field-based scenarios. This study found similar estimates for sensitivity and specificity as reported by Addisu et al (15). However, our work is the first to conduct a complete systematic review approach through a comprehensive search and selection, a random model meta-analysis, risk of bias assessment, and certainty of evidence using the GRADE approach and following the methods recommended by the Cochrane collaboration.…”

“…Despite the recommendation for PoC quantitative or semi-quantitative testing before administering antimalarial treatment, there is only one synthesis of the diagnostic test accuracy (DTA) of the STANDARD G6PD TM test manufactured by SD Biosensor (StandG6PD-BS) (15) in which the authors pooled the individual results of various studies without a complete systematic review approach, risk of bias, and certainty of evidence assessment. In this systematic review and metanalysis, we estimated the pooled DTA of the StandG6PD-BS for different thresholds of G6PD activity.…”

Associations between COVID-19 and Glucose-6-Phosphate Dehydrogenase Activity in Brazil

“…57 In our study, G6PD activity was determined using validated system SD Biosensor STANDARD G6PD V R equipment, discriminating G6PDd from G6PDn, and defining the enzyme activity quantitatively. 46 We evidenced a much greater prevalence of G6PDd (16.3%) in patients with COVID-19 when compared with another study carried out in Manaus. 54 High prevalence was also observed in a study conducted in Sardinia, Italy, showing that the frequency of patients with G6PDd was greater among patients with COVID-19 compared with the health population.…”

“…On day 1 and 1 year from infection, the measurement of G6PD enzyme activity, and G6PD and hemoglobin occurred using SD Biosensor STANDARD G6PD V R equipment (Gyeonggi-do, Republic of Korea). 46 According to the activity of the G6PD enzyme, patients were divided into two groups: G6PDd (activity ,4) and G6PDn (activity $4). 47 Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon 48,49 (s1050828, rs1050829 and rs5030868), corresponding to G6PD African A-(G202A, A376G), G6PD African A1 (A376G), and G6PD Mediterranean (C563T), respectively.…”